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Licensed Unlicensed Requires Authentication Published by De Gruyter June 2, 2015

C-reactive protein and inflammation: conformational changes affect function

Yi Wu, Lawrence A. Potempa, Driss El Kebir and János G. Filep
From the journal Biological Chemistry

Abstract

The prototypic acute-phase reactant C-reactive protein (CRP) has long been recognized as a useful marker and gauge of inflammation. CRP also plays an important role in host defense against invading pathogens as well as in inflammation. CRP consists of five identical subunits arranged as a cyclic pentamer. CRP exists in at least two conformationally distinct forms, i.e. native pentameric CRP (pCRP) and modified/monomeric CRP (mCRP). These isoforms bind to distinct receptors and lipid rafts, and exhibit distinct functional properties. Dissociation of pCRP into its subunits occurs within the inflammatory microenvironment and newly formed mCRP may then contribute to localizing the inflammatory response. Accumulating evidence indicates that pCRP possesses both pro- and anti-inflammatory actions in a context-dependent manner, whereas mCRP exerts potent pro-inflammatory actions on endothelial cells, endothelial progenitor cells, leukocytes and platelets, and thus may amplify inflammation. Here, we review recent advances that may explain how conformational changes in CRP contribute to shaping the inflammatory response and discuss CRP isomers as potential therapeutic targets to dampen inflammation.


Corresponding author: János G. Filep, Research Center, Maisonneuve-Rosemont Hospital and Department of Pathology and Cell Biology, University of Montréal, 5415 boulevard de l’Assomption, Montréal H1T 2M4, QC, Canada, e-mail:

Acknowledgments

The authors apologize to those whose articles have not been cited due to space limitations. This work was supported by grants from the Canadian Institutes of Health Research (MOP-64283, MOP-94851 and MOP-102619 to J.G.F.) and the National Science Foundation of China-Canadian Institutes of Health Research (CCI-85707 and 30711120578 to Y.W. and J.G.F.).

References

Abernathy, T.J. and Avery, O.T. (1941). The occurrence during acute infections of a protein not normally present in the blood: I. Distribution of the reactive protein in patients’ sera and the effect of calcium on the flocculation reaction with C-polysaccharide of pneumococcus. J. Exp. Med. 73, 173–182.10.1084/jem.73.2.173Search in Google Scholar PubMed PubMed Central

Agrawal, A., Shrive, A.K., Greenhough, T.J., and Volanakis, J.E. (2001). Topology and structure of the C1q-binding site on C-reactive protein. J. Immunol. 166, 3998–4004.10.4049/jimmunol.166.6.3998Search in Google Scholar PubMed

Ahrens, I., Domeij, H., Eisenhardt, S.U., Topcic, D., Albrecht, M., Leitner, E., Viitaniemi, K., Jowett, J.B., Lappas, M., Bode, C., et al. (2011). Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells. Basic Res. Cardiol. 106, 879–895.10.1007/s00395-011-0191-ySearch in Google Scholar PubMed PubMed Central

Asztalos B.F., Horan, M.S., Horvath, K.V., Mcdermott, A.Y., Chalasani, N.P., and Schaefer, E.J. (2014). Obesity associated molecular forms of C-reactive protein in human. PLoS One 9, e109238.10.1371/journal.pone.0109238Search in Google Scholar PubMed PubMed Central

Bang, R., Marnell, L., Mold, C., Stein, M.-P., Du Clos, K.T., Chivington-Buck, C., and Du Clos, T.W. (2005). Analysis of binding sites in human C-reactive protein for FcγRI, FcγRIIA, and C1q by site-directed mutagenesis. J. Biol. Chem. 280, 25095–25102.10.1074/jbc.M504782200Search in Google Scholar PubMed

Bharadwaj, D., Stein, M.-P., Volzer, M.A., Burlingame, R.W., and Du Clos, T.W. (1999). The major receptor for C-reactive protein on leukocytes is Fcγ receptor II. J. Exp. Med. 190, 585–590.10.1084/jem.190.4.585Search in Google Scholar PubMed PubMed Central

Bisoendial, R.J., Kastelein, J.J., Levels, J.H., Zwaginga, J.J., van den Bogaard, B., Reitsma, P.H., Meijers, J.C., Hartman, D., Levi, M., and Stroes, E.S. (2005). Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ. Res. 96, 714–716.10.1161/01.RES.0000163015.67711.ABSearch in Google Scholar PubMed

Bisoendial, R.J., Kastelein, J.J., Peters, S.L., Levels, J.H., Birjmohun, R., Rotmans, J.I., Hartman, D., Meijers, J.C., Levi, M., and Stroes, E.S. (2007). Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects. J. Lipid Res. 48, 952–960.10.1194/jlr.P600014-JLR200Search in Google Scholar PubMed

Black, S., Kushner, I., and Samols, D. (2004). C-reactive protein. J. Biol. Chem. 279, 48487–48490.10.1074/jbc.R400025200Search in Google Scholar PubMed

Brennan, M.P., Moriarty, R.D., Grennan, S., Chubb, A.J., and Cox, D. (2008) C-reactive protein binds to αIIbβ3. J. Thromb. Haemost. 6, 1239–1241.10.1111/j.1538-7836.2008.02993.xSearch in Google Scholar PubMed

Calabro, P., Willerson, J.T., and Yeh, E.T. (2003). Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation 108, 1930–1932.10.1161/01.CIR.0000096055.62724.C5Search in Google Scholar PubMed

Casas, J.P., Shah, T., Hingorani, A.D., Danesh, J., and Pepys, M.B. (2008). C-reactive protein and coronary heart disease: a critical review. J. Intern. Med. 264, 295–314.10.1111/j.1365-2796.2008.02015.xSearch in Google Scholar PubMed

Chang, M.K., Binder, C.J., Torzewski, M., and Witztum, J. (2002). C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc. Natl. Acad. Sci. USA 99, 13043–13048.10.1073/pnas.192399699Search in Google Scholar PubMed PubMed Central

Chen, J., Huang, L., Song, M., Yu, S., Gao, P., and Jing, J. (2009). C-reactive protein upregulates receptor for advanced glycation end products expression and alters antioxidant defenses in rat endothelial progenitor cells. J. Cardiovasc. Pharmacol. 53, 359–367.10.1097/FJC.0b013e31819b5438Search in Google Scholar PubMed

Ciubotaru, I., Potempa, L.A., and Wander, R.C. (2005). Production of modified C-reactive protein in U937-derived macrophages. Exp. Biol. Med. (Maywood) 230, 762–770.10.1177/153537020523001010Search in Google Scholar PubMed

Crawford, D.C., Sanders, C.L., Qin, X., Smith, J.D., Shephard, C., Wong, M., Witrak, L., Rieder, M.J., and Nickerson, D.A. (2006). Genetic variation is associated with C-reactive protein levels in the third national health and nutrition examination survey. Circulation 114, 2458–2465.10.1161/CIRCULATIONAHA.106.615740Search in Google Scholar PubMed

C-Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC), Wensley, F., Gao, P., Burgess, S., Kaptoge, S., Di Angelantonio, E., Shah, T., Engert, J.C., Clarke, R., Davey-Smith, G., et al. (2011) Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. Br. Med. J. 342, d548.10.1136/bmj.d548Search in Google Scholar PubMed PubMed Central

Devaraj, S. and Jialal, I. (2011). C-reactive protein polarizes human macrophages to an M1 phenotype and inhibits transformation to the M2 phenotype. Arterioscler. Thromb. Vasc. Biol. 31, 1397–1402.10.1161/ATVBAHA.111.225508Search in Google Scholar PubMed PubMed Central

Devaraj, S., Xu, D.Y., and Jialal, I. (2003). C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: Implications for the metabolic syndrome and atherothrombosis. Circulation 107, 398–404.10.1161/01.CIR.0000052617.91920.FDSearch in Google Scholar PubMed

Devaraj, S., Du Clos, T.W., and Jialal, I. (2005). Binding and internalization of C-reactive protein by Fc gamma receptors on human aortic endothelial cells mediates biological effects. Arterioscler. Thromb. Vasc. Biol. 25, 1359–1363.10.1161/01.ATV.0000168573.10844.aeSearch in Google Scholar PubMed

Devaraj, S., Davis, B., Simon, S.I., and Jialal, I. (2006). CRP promotes monocyte-endothelial cell adhesion via Fcγ receptors in human aortic endothelial cells under static and shear flow conditions. Am. J. Physiol. Heart Circ. Physiol. 291, H1170–H1176.10.1152/ajpheart.00150.2006Search in Google Scholar PubMed

Diehl, E.E., Haines, G.K. III, Radosevich, J.A., and Potempa, L.A. (2000). Immunohistochemical localization of modified C-reactive protein antigen in normal vascular tissue. Am. J. Med. Sci. 319, 79–83.10.1097/00000441-200002000-00002Search in Google Scholar PubMed

El Kebir, D., Zhang, Y., Potempa, L.A., Wu, Y., Fournier, A., and Filep, J.G. (2011). C-reactive protein-derived peptide 201–206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32. J. Leukoc. Biol. 90, 1167–1175.10.1189/jlb.0111032Search in Google Scholar PubMed

Eisenhardt, S.U., Habersberger, J., Murphy, A., Chen, Y.C., Woollard, K.J., Bassler, N., Qian, H., von zur Muhlen, C., Hagemeyer, C.E., Ahrens, I., et al. (2009). Dissociation of pentameric to monomeric C-reactive protein on activated platelets localizes inflammation to atherosclerotic plaques. Circ. Res. 105, 128–137.10.1161/CIRCRESAHA.108.190611Search in Google Scholar PubMed

Fadi, G., Oparil, S., Xing, D., Chen, Y.-F., McCrory, M.A., and Szalai, A.J. (2010). C-reactive protein-mediated vascular injury requires complement. Arterioscler. Thromb. Vasc. Biol. 30, 1189–1195.10.1161/ATVBAHA.110.205377Search in Google Scholar PubMed PubMed Central

Filep, J.G. (2009). Platelets affect the structure and function of C-reactive protein. Circ. Res. 105, 109–111.10.1161/CIRCRESAHA.109.202010Search in Google Scholar PubMed

Filep, J.G. and El Kebir, D. (2009). Neutrophil apoptosis: a target for enhancing the resolution of inflammation. J. Cell. Biochem. 108, 1039–1046.10.1002/jcb.22351Search in Google Scholar PubMed

Fu, T. and Borensztajn, J. (2002). Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions. Biochem. J. 366, 195–201.10.1042/bj20020045Search in Google Scholar PubMed PubMed Central

Fujii, H., Li, S.H., Szmitko, P.E., Fedak, P.W., and Verma, S. (2006). C-reactive protein alters antioxidant defenses and promotes apoptosis in endothelial progenitor cells. Arterioscler. Thromb. Vasc. Biol. 26, 2476–2482.10.1161/01.ATV.0000242794.65541.02Search in Google Scholar PubMed

Fujita, Y., Kakino, A., Nishimichi, N., Yamaguchi, S., Sato, Y., Machida, S., Cominacini, L., Delneste, Y., Matsuda, H., and Sawamura, T. (2009). Oxidized LDL receptor LOX-1 binds to C-reactive protein and mediates its vascular effects. Clin. Chem. 55, 285–294.10.1373/clinchem.2008.119750Search in Google Scholar PubMed

Fujita, M., Takada, Y.K., Izumiya, Y., and Takada, Y. (2014). The binding of monomeric C-reactive protein (mCRP) to integrins αVβ3 and α4β1 is related to its pro-inflammatory action. PLoS One 9, e93738.10.1371/journal.pone.0093738Search in Google Scholar PubMed PubMed Central

Gabay, C. and Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340, 448–454.10.1056/NEJM199902113400607Search in Google Scholar PubMed

Gershov, D., Kim, S.J., Brot, N., and Elkon, K.B. (2000) C-reactive protein binds to apoptotic cells, protects the cells from the assembly of the terminal complement components, and sustains an antiinflamamtory innate immune response. J. Exp. Med. 192, 1353–1364.Search in Google Scholar

Gill, R., Kemp, J.A., Sabin, C., and Pepys, M.B. (2004). Human C-reactive protein increases cerebral infarct size after middle cerebral artery occlusion in adult rats. J. Cereb. Blood Flow Metab. 24, 1214–1218.10.1097/01.WCB.0000136517.61642.99Search in Google Scholar PubMed

Griselli, H., Herbert, J., Hutchinson, W.L., Taylor, K.M., Sohail, M., Krausz, T., and Pepys, M.B. (1999). C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J. Exp. Med. 190, 1733–1740.10.1084/jem.190.12.1733Search in Google Scholar PubMed PubMed Central

Habersberger, J., Strang, F., Scheichl, A., Htun, N., Bassler, N., Merivirta, R.-M., Diehl, P., Krippner, G., Meikle, P., Eisenhardt, S.U., et al. (2012). Circulating microparticles generate and transport monomeric C-reactive protein in patients with myocardial infarction. Cardiovasc. Res. 96, 64–72.10.1093/cvr/cvs237Search in Google Scholar PubMed

Hage, F.G., Oparil, S., Xing, D., Chen, Y.-F., McCrory, M.A., and Szalai, A.J. (2010). C-reactive protein-mediated vascular injury requires complement. Arterioscler. Thromb. Vasc. Biol. 30, 1189–1195.10.1161/ATVBAHA.110.205377Search in Google Scholar PubMed PubMed Central

Hammond, D.J. Jr., Singh, S.K., Thompson, J.A., Beeler, B.W., Rusinol, A.E., Pangburn, M.K., Potempa, L.A., and Agrawal, A. (2010). Identification of acidic pH-dependent ligands of pentameric C-reactive protein. J. Biol. Chem. 285, 36235–36244.10.1074/jbc.M110.142026Search in Google Scholar PubMed PubMed Central

Han, K.H., Hong, K.H., Park, J.H., Ko, J., Kang, D.H., Choi, K.J., Hong, M.K., Park, S.W., and Park, S.J. (2004). C-reactive protein promotes monocyte chemoattractant protein-1-mediated chemotaxis through up-regulating CC chemokine receptor 2 expression in human monocytes. Circulation 109, 2566–2571.10.1161/01.CIR.0000131160.94926.6ESearch in Google Scholar PubMed

Hanriot, D., Bello, G., Ropars, A., Seguin-Devaux, C., Poitevin, G., Grosjean, S., Latger-Cannard, V., Devaux, Y., Zanmad, F., Regnault, V., et al. (2008). C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor α, on human monocytes. Thromb. Haemost. 99, 558–569.10.1160/TH07-06-0410Search in Google Scholar PubMed

Hanson, K.G. and Libby, P. (2006). The immune response in atherosclerosis: a double-edged sword. Nat. Rev. Immunol. 6, 508–519.10.1038/nri1882Search in Google Scholar PubMed

Heuertz, R.M., Ahmed, N., and Webster, R.O. (1996). Peptides derived from C-reactive protein inhibit neutrophil alveolitis. J. Immunol. 156, 3412–3417.Search in Google Scholar

Heuertz, R.M., Schneider, G.P., Potempa, L.A., and Webster, R.O. (2005). Native and modified C-reactive proteins bind different receptors on human neutrophils. Int. J. Biochem. Cell Biol. 37, 320–335.10.1016/j.biocel.2004.07.002Search in Google Scholar PubMed

Hill, J.M., Zalos, G., Halcox, J.P., Schenke, W.H., Waclawiw, M.A., Quyyumi, A.A., and Finkel, T. (2003). Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593–600.10.1056/NEJMoa022287Search in Google Scholar PubMed

Hirschfield, G.M., Gallimore, J.R., Kahan, M.C., Hutchinson, W.L., Sabin, C.A., Benson, G.M., Dhillon, A.P., Tennent, G.A., and Pepys, M.B. (2005). Transgenic human C-reactive protein is not proatherogenic in apoplipoprotein E-deficient mice. Proc. Natl. Acad. Sci. USA 102, 8309–8014.10.1073/pnas.0503202102Search in Google Scholar PubMed PubMed Central

Jabs, W.J., Lögering, B.A., Gerke, P., Kreft, B., Wolber, E.M., Klinger, M.H., Fricke, L., and Steinhoff, J. (2003a). The kidney as a second site of human C-reactive protein formation in vivo. Eur. J. Immunol. 33, 152–161.10.1002/immu.200390018Search in Google Scholar PubMed

Jabs, W.J., Theissing, E., Nitschke, M., Bechtel, J.F., Duchrow, M., Mohamed, S., Jahrbeck, B., Sievers, H.H., Steinhoff, J., and Bartels, C. (2003b). Local generation of C-reactive protein in diseased coronary artery venous bypass grafts and normal tissue. Circulation 108, 1428–1431.10.1161/01.CIR.0000092184.43176.91Search in Google Scholar PubMed

Ji, S.-R., Wu, Y., Potempa, L.A., Liang, Y.-H., and Zhao, J. (2006a) Effect of modified C-reactive protein on complement activation. Arterioscler. Thromb. Vasc. Biol. 26, 935–941.10.1161/01.ATV.0000206211.21895.73Search in Google Scholar PubMed

Ji, S.R. Wu, Y., Potempa, L.A., Qiu, Q., and Zhao, J. (2006b). The interactions of low density lipoprotein with different forms of C-reactive protein: implication of an active role of modified C-reactive protein in the pathogenesis of atherosclerosis. Int. J. Biochem. Cell Biol. 38, 648–661.10.1016/j.biocel.2005.11.004Search in Google Scholar PubMed

Ji, S.-R., Wu, Y., Zhu, L., Potempa, L.A., Sheng, F.L., Lu, W., and Zhao, J. (2007). Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate mCRP(m). FASEB J. 21, 284–294.10.1096/fj.06-6722comSearch in Google Scholar PubMed

Ji, S.-R., Ma, L., Bai, C.J., Shi, J.M., Li, H.Y., Potempa, L.A., Filep, J.G., Zhao, J., and Wu, Y. (2009). Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft micro-domains. FASEB J. 23, 1806–1816.10.1096/fj.08-116962Search in Google Scholar PubMed

Kakuta, Y., Aoshiba, K., and Nagai, A. (2006). C-reactive protein products generated by neutrophil elastase promote neutrophils apoptosis. Arch Med. Res. 37, 456–460.10.1016/j.arcmed.2005.10.010Search in Google Scholar PubMed

Kaplan, M.J. (2009). Premature vascular damage in systemic lupus erythematosus. Autoimmunity 42, 580–586.10.1080/08916930903002479Search in Google Scholar

Kapur, R., Heitink-Pollé, K.M.J., Porcelijn, L., Bentlage, A.E.H., Bruin, M.C.A., Visser, R., Roos, D., Schasfoort, R.B.M., de Haas, M., van der Schoot, E., et al. (2015). C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia. Blood 125, 1793–1802.10.1182/blood-2014-05-579110Search in Google Scholar

Kardys, I., de Maat, M.P., Uitterlinden, A.G., Hofman, A., and Witteman, J.C. (2006). C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam study. Eur. Heart J. 27, 1331–1337.10.1093/eurheartj/ehl018Search in Google Scholar

Khreiss, T., József, L., Hossain, S., Chan, J.S.D., Potempa, L.A., and Filep, J.G. (2002). Loss of pentameric symmetry of C-reactive protein is associated with delayed apoptosis of human neutrophils. J. Biol. Chem. 277, 40775–40781.10.1074/jbc.M205378200Search in Google Scholar

Khreiss, T., József, L., Potempa, L.A., and Filep, J.G. (2004a). Conformational rearrangement in C-reactive protein is required for proinflammatory actions on human endothelial cells. Circulation 109, 2016–2022.10.1161/01.CIR.0000125527.41598.68Search in Google Scholar

Khreiss, T., József, L., Potempa, L.A., and Filep, J.G. (2004b). Opposing effects of C-reactive protein isoforms on shear-induced neutrophil-platelet adhesion and neutrophil aggregation in whole blood. Circulation 110, 2713–2720.10.1161/01.CIR.0000146846.00816.DDSearch in Google Scholar

Khreiss, T., József, L., Potempa, L.A., and Filep, J.G. (2005). Loss of pentameric symmetry in C-reactive protein induces interleukin-8 secretion through peroxynitrite signalling in human neutrophils. Circ. Res. 97, 690–697.10.1161/01.RES.0000183881.11739.CBSearch in Google Scholar

Koenig, W. (2013). High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int. J. Cardiol. 168, 5126–5134.10.1016/j.ijcard.2013.07.113Search in Google Scholar

Kovacs, A., Tornwall, P., Nilsson, R., Tegner, J., Hamsten, A., and Bjorkegren, J. (2007). Human C-reactive protein slows atherosclerosis development in a mouse model with human-like hypercholesterolemia. Proc. Natl. Acad. Sci. USA 104, 13768–13773.10.1073/pnas.0706027104Search in Google Scholar

Kresl, J.J., Potempa, L.A., and Anderson, B.E. (1998). Conversion of native oligomeric to a modified monomeric form of human C-reactive protein. Int. J. Biochem. Cell Biol. 30, 1415–1426.10.1016/S1357-2725(98)00078-8Search in Google Scholar

Krijnen, P.A., Ciurana, C., Cramer, T., Hazes, T., Meijer, C.J., Visser, C.A., Niessen, H.W., and Hack, C.E. (2005). IgM colocalizes with complement and C-reactive protein in infarcted myocardium. J. Clin. Pathol. 58, 382–388.10.1136/jcp.2004.022988Search in Google Scholar PubMed PubMed Central

Lane, T., Wassef, N., Poole, S., Mistry, Y., Lachmann, H.J., Gillmore, J.D., Hawkins, P.N., and Pepys, M.B. (2014). Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers. Circ. Res. 114, 672–676.10.1161/CIRCRESAHA.114.302770Search in Google Scholar PubMed

Ley, K., Laudanna, C., Cybulsky, M.I., and Noursargh, S. (2007). Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7, 678–689.10.1038/nri2156Search in Google Scholar PubMed

Li, L., Roumeliotis, N., Sawamura, T., and Renier, G. (2004a). C-reactive protein enhances LOX-1 expression in human aortic endothelial cells: relevance of LOX-1 to C-reactive protein-induced endothelial dysfunction. Circ. Res. 95, 877–883.10.1161/01.RES.0000147309.54227.42Search in Google Scholar PubMed

Li, S.H., Szmitko, P.E., Weisel, R.D., Wang, C.H., Fedak, P.W., Li, R.K., Mickle, D.A., and Verma, S. (2004b). C-reactive protein upregulates complement-inhibitory factors in endothelial cells. Circulation 109, 833–836.10.1161/01.CIR.0000117087.27524.0ESearch in Google Scholar PubMed

Li, R., Ren, M., Luo, M., Chen, N., Zhang, Z., Luo, B., and Wu, J. (2012). Monomeric C-reactive protein alters fibrin clot properties on endothelial cells. Thromb. Res. 129, e251–e256.10.1016/j.thromres.2012.03.014Search in Google Scholar PubMed

Li, H.-Y., Wang, J., Wu, Y.-X., Zhang, L., Liu, Z.-P., Filep, J.G., Potempa, L.A., Wu, Y., and Ji, S.-R. (2014). Topological localization of monomeric C-reactive protein determines pro-inflammatory endothelial cell responses. J. Biol. Chem. 289, 14283–14290.10.1074/jbc.M114.555318Search in Google Scholar PubMed PubMed Central

Lu, J., Marnell, L.L., Marjon, K.D., Mold, C., Du Clos, T.W., and Sun, P.D. (2008). Structural recognition and functional activation of FcγR by innate pentraxins. Nature 456, 989–993.10.1038/nature07468Search in Google Scholar PubMed PubMed Central

Lu, J., Marjon, K.D., Marnell, L.L., Wang, R., Mold, C., Du Clos, T.W., and Sun P (2011). Recognition and functional activation of the human IgA receptor (FcalphaRI) by C-reactive protein. Proc. Natl. Acad. Sci. USA 108, 4974–4979.10.1073/pnas.1018369108Search in Google Scholar PubMed PubMed Central

Marnell, L.L., Mold, C., Volzer, M.A., Burlingame, R.W., and Du Clos, T.W. (1995). C-reactive protein binds to FcγRI in transfected COS cells. J. Immunol. 155, 2185–2193.Search in Google Scholar

Marnell, L.L., Mold, C., and Du Clos, T.W. (2005). C-reactive protein: ligands, receptors and role in inflammation. Clin. Immunol. 117, 104–111.10.1016/j.clim.2005.08.004Search in Google Scholar PubMed

Mihlan, M., Blom, A.M., Kupreishvili, K., Lauer, N., Stelzner, K., Bergström, F., Niessen, H.W.M., and Zipfel, P.F. (2011). Monomeric C-reactive protein modulates classic complement activation on necrotic cells. FASEB J. 25, 4198–4210.10.1096/fj.11-186460Search in Google Scholar PubMed

Mold, C., Rodic-Polic, B., and Du Clos, T.W. (2002). Protection from Streptococcus pneumoniae infection by C-reactive protein and natural antibody requires complement but not Fcgamma receptors. J. Immunol. 168, 6375–6381.10.4049/jimmunol.168.12.6375Search in Google Scholar PubMed

Molins, B., Peña, E., Vilahur, G., Mandieta, C., Slevin, M., and Badimon, L. (2008). C-reactive protein isoforms differ in their effects on thrombus growth. Arterioscler. Thromb. Vasc. Biol. 28, 2239–2246.10.1161/ATVBAHA.108.174359Search in Google Scholar PubMed

Molins, B., Peña, E., de la Torre, R., and Badimon, L. (2011) Monomeric C-reactive protein is prothrombotic and dissociates from circulating pentameric C-reactive protein on adhered activated platelets under flow. Cardiovasc. Res. 92, 328–337.10.1093/cvr/cvr226Search in Google Scholar PubMed

Montecucco, F., Steffens, S., Burger, F., Pelli, G., Monaco, C., and Mach, F. (2008). C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes. J. Leukoc. Biol. 84, 1109–1119.10.1189/jlb.0208123Search in Google Scholar PubMed

Monteiro, R.C. and van den Winkel, J.G. (2003). IgA Fc receptors. Annu. Rev. Immunol. 21, 177–204.10.1146/annurev.immunol.21.120601.141011Search in Google Scholar PubMed

Murray, P.J. and Wynn, T.A. (2011). Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737.10.1038/nri3073Search in Google Scholar PubMed PubMed Central

Nathan, C. and Ding, A. (2010). Nonresolving inflammation. Cell 140, 871–882.10.1016/j.cell.2010.02.029Search in Google Scholar PubMed

Nimmerjahn, F. and Ravetch, J.V. (2008). Fcγ receptors as regulators of immune responses. Nat. Rev. Immunol. 8, 34–47.10.1038/nri2206Search in Google Scholar PubMed

Noveck, R., Stroes, E.S.G., Flaim, J.D., Baker, B.F., Hughes, S., Graham, M.J., Crooke, R.M., and Ridker, P.M. (2014). Effects of an antisense oligonucleotide inhibitor of C-reactive protein synthesis on the endotoxin challenge response in healthy human male volunteers. J. Am. Heart Assoc. 3, pii: e001084. doi:10.1161/JAHA.114.001084.10.1161/JAHA.114.001084Search in Google Scholar PubMed PubMed Central

Okemefuna, A.I., Stach, L., Rana, S., Buetas, A.J., Gor, J., and Perkins, S.J. (2010). C-reactive protein exists in an NaCl concentration-dependent pentamer-decamer equilibrium in physiological buffer. J. Biol. Chem. 285, 1041–1052.10.1074/jbc.M109.044495Search in Google Scholar

Pasceri, V., Willerson, J.T., and Yeh, E.T. (2000). Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102, 2165–2168.10.1161/01.CIR.102.18.2165Search in Google Scholar

Pasceri, V., Cheng, J.S., Willerson, J.T., and Yeh, ET. (2001). Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103, 2531–2534.10.1161/01.CIR.103.21.2531Search in Google Scholar

Paul, A., Ko, K.W., Li, L., Yechoor, V., McCrory, M.A., Szalai, A.J., and Chan, L. (2004). C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation 109, 647–655.10.1161/01.CIR.0000114526.50618.24Search in Google Scholar

Pepys, M.B. and Hirschfield, G.M. (2003) C-reactive protein: a critical update. J. Clin. Invest. 111, 805–1812.10.1172/JCI200318921Search in Google Scholar

Pepys, M.B., Hirschfield, G.M., Tennent, G.A., Gallimore, J.R., Kahan, M.C., Bellotti, V., Hawkins, P.N., Myers, R.M., Smith, M.D., Polara, A., et al. (2006). Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 440, 1217–1221.10.1038/nature04672Search in Google Scholar

Perkins, S.J., Okemefuna, A.I., and Nan, R. (2010) Unravelling protein-protein interactions between complement factor H and C-reactive protein using a multidisciplinary strategy. Biochem. Soc. Trans. 38, 894–900.Search in Google Scholar

Pober, J.S. and Sessa, W.C. (2007). Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7, 803–815.10.1038/nri2171Search in Google Scholar

Potempa, L.A., Maldonado, B.A., Laurent, P., Zemel, E.S., and Gewurz, H. (1983). Antigenic, electrophoretic and binding alterations of human C-reactive protein modified selectively in the absence of calcium. Mol. Immunol. 20, 1165–1175.10.1016/0161-5890(83)90140-2Search in Google Scholar

Qamirani, E., Ren, Y., Kuo, L., and Hein, T.W. (2005). C-reactive protein inhibits endothelium–dependent NO-mediated dilation in coronary arterioles by activating p38 kinase and NAD(P)H oxidase. Arterioscler. Thromb. Vasc. Biol. 25, 995–1001.10.1161/01.ATV.0000159890.10526.1eSearch in Google Scholar PubMed

Reynolds, G.D. and Vance, R.P. (1987) C-reactive protein immunohistochemical localization in normal and atherosclerotic human aortas. Arch. Pathol. Lab. Med. 111, 265–269.Search in Google Scholar

Rodriguez, W., Mold, C., Kataranovski, M., Hutt, J.A., Marnell, L.L., Verbeek, J.S., and Du Clos T.W. (2007). C-reactive protein-mediated suppression of nephrotoxic nephritis: role of macrophages, complement, and Fcγ receptors. J. Immunol. 178, 530–538.10.4049/jimmunol.178.1.530Search in Google Scholar PubMed

Russell, A.I., Cunninghame Graham, D.S., Shepherd, C., Roberton, C.A., Whittaker, J., Meeks, J., Powell, R.J., Isenberg, D.A., Walport, M.J., and Vyse, T.J. (2004). Polymorphism in the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum. Mol. Genet. 13, 137–147.10.1093/hmg/ddh021Search in Google Scholar PubMed PubMed Central

Schwartz, R., Osborne-Lawrence, S., Hahner, L., Gibson, L.H., Gormley, A.K., Vongpatanasin, W., Zhu, W., Word, A., Seetharam, D., Black, S., et al. (2007). C-reactive protein downregulates endothelial NO synthase and attenuates reendothelialization in vivo in mice. Circ. Res. 100, 1452–1459.10.1161/01.RES.0000267745.03488.47Search in Google Scholar PubMed

Schwedler, S.B., Guderian, F., Dammrich, J., Potempa, L.A., and Wanner, C. (2003). Tubular staining of modified C-reactive protein in diabetic chronic kidney disease. Nephrol. Dial. Transplant. 18, 2300–2307.10.1093/ndt/gfg407Search in Google Scholar PubMed

Schwedler, S.B., Amann, K., Wernicke, K., Krebs, A., Nauck, M., Wanner, C., Potempa, L.A., and Galle, J. (2005). Native C-reactive protein increases whereas modified C-reactive protein reduces atherosclerosis in apolipoprotein E-knockout mice. Circulation 112, 1016–1023.10.1161/CIRCULATIONAHA.105.556530Search in Google Scholar PubMed

Schwedler, S.B., Filep, J.G., Galle, J., Wanner, C., and Potempa, L.A. (2006). C-reactive protein: a family of proteins to regulate cardiovascular function. Am. J. Kidney Dis. 47, 212–222.10.1053/j.ajkd.2005.10.028Search in Google Scholar PubMed

Schwedler, S.B., Kuhlencordt, P.J., Ponnuswamy, P.P., Hatiboglu, G., Quaschning, T., Widder, J., Wanner, C., Potempa, L.A., and Galle, J. (2007). Native C-reactive protein induces endothelial dysfunction in ApoE-/- mice: implications of iNOS and reactive oxygen species. Atherosclerosis 195, e76–e84.10.1016/j.atherosclerosis.2007.06.013Search in Google Scholar PubMed

Schwedler, S.B., Hansen-Hagge, T., Reichert, M., Schmiedeke, D., Schneider, R., Galle, J., Potempa, L.A., Wanner, C., and Filep, J.G. (2009). Monomeric C-reactive protein decreases acetylated LDL uptake in human endothelial cells. Clin. Chem. 55, 1728–1731.10.1373/clinchem.2009.125732Search in Google Scholar PubMed

Scirica, B.M. and Morrow, D.A. (2006). Is C-reactive protein an innocent bystander of proatherogenic culprit? Circulation 113, 2128–2134.10.1161/CIRCULATIONAHA.105.611350Search in Google Scholar PubMed

Scott, J. (2007). The liver X receptor and atherosclerosis. N. Engl. J. Med. 357, 2195–2197.10.1056/NEJMcibr075951Search in Google Scholar PubMed

Shephard, E.G., Anderson, R., Rosen, O., Myer, M.S., Friedkin, M., Strachan, A.F., and de Beer, F.C. (1990). Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis. J. Immunol. 145, 1469–1476.Search in Google Scholar

Shrive, A.K., Cheetham, M., Holden, D., Myles, D.A., Turnell, W.G., Volanakis, J.E., Pepys, M.B., Bloomer, A.C., and Greenhough, T.J. (1996). Three dimensional structure of human C-reactive protein. Nat. Struct. Biol. 3, 346–354.10.1038/nsb0496-346Search in Google Scholar PubMed

Sica, A. and Mantovani, A. (2012). Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787–795.10.1172/JCI59643Search in Google Scholar

Singh, U., Devaraj, S., Dasu, M.R., Ciobanu, D., Reusch, J., and Jialal, I. (2006) C-reactive protein decreases interleukin-10 secretion in activated human monocyte-derived macrophages via inhibition of cyclic AMP production. Arterioscler. Trhomb. Vasc. Biol. 26, 2469–2475.Search in Google Scholar

Singh, S.K., Suresh, M.V., Prayhter, D.C., Moorman, J.P., Rusinol, A.E. and Agrawal, A. (2008). C-reactive protein-bound enzymatically modified low-density lipoprotein does not transform macrophages into foam cells. J. Immunol. 180, 4316–4322.10.4049/jimmunol.180.6.4316Search in Google Scholar

Sjöberg, A.P., Trouw, L.A., McGrath, F.D., Hack, C.E., and Blom, A.M. (2006). Regulation of complement activation by C-reactive protein: targeting of the inhibitory activity of C4b-binding protein. J. Immunol. 176, 7612–7620.10.4049/jimmunol.176.12.7612Search in Google Scholar

Sjöwall, C., Bengtsson, A.A., Sturfelt, G., and Skogh, T. (2004). Serum levels of autoantibodies against monomeric C-reactive protein are correlated with disease activity in systemic lupus erythematosus. Arthritis res. Ther. 6, R87–R94.10.1186/ar1032Search in Google Scholar

Slevin, M., Matou-Nasri, S., Turu, M., Luque, A., Rovira, N., Badimon, L., Boluda, S., Potempa, L.A., Sanfeliu, C., de Vera, N., et al. (2010). Modified C-reactive protein is expressed by stroke neovessels and is a potent activator of angiogenesis in vitro. Brain Pathol. 20, 151–165.10.1111/j.1750-3639.2008.00256.xSearch in Google Scholar

Sreeramkumar, V., Adrover, J.M., Ballesteros, I., Cuartero, M.I., Rossaint, J., Bilbao, I., Nácher, M., Pitaval, C., Radovanovic, I., Fukui, Y., et al. (2014). Neutrophils scan for activated platelet to initiate inflammation. Science 346, 1234–1238.10.1126/science.1256478Search in Google Scholar

Stein, M.P., Edberg, J.C., Kimberly, R.P., Mangan, E.K., Bharadwaj, D., Mold, C., and Du Clos, T.W. (2000). C-reactive protein binding to FcγRIIa on human monocyte sand neutrophils is allele-specific. J. Clin. Invest. 105, 369–376.10.1172/JCI7817Search in Google Scholar

Sternik, L., Samee, S., Schaff, H.V., Zehr, K.J., Lerman, L.O., Holmes, D.R., Hermann, J., and Lerman, A. (2002). C-reactive protein relaxes human vessels in vitro. Arterioscler. Thromb. Vasc. Biol. 22, 1865–1868.10.1161/01.ATV.0000033821.96354.90Search in Google Scholar

Strang, F., Scheichl, A., Chen, Y.C., Wang, X., Htun, N.M., Bassler, N., Eisenhardt, S.U., Habersberger, J., and Peter, K. (2012). Amyloid plaques dissociate pentameric to monomeric C-reactive protein: a novel pathomechanism driving cortical inflammation in Alzheimer’s disease? Brain Pathol. 22, 337–346.Search in Google Scholar

Sun, H., Koike, T., Ichikawa, T., Hatakeyama, K., Shiomi, M., Zhang, B., Kitajima, S., Morimoto, M., Watanabe, T., Asada, Y., et al. (2005). C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance. Am. J. Pathol. 167, 1139–1148.10.1016/S0002-9440(10)61202-3Search in Google Scholar

Szalai, A.J., Nataf, S., Hu, X.Z., and Barnum, S.R. (2002). Experimental allergic encephalomyelitis is inhibited in transgenic mice expressing human C-reactive protein. J. Immunol. 168, 5792–5797.10.4049/jimmunol.168.11.5792Search in Google Scholar PubMed

Szalai, A.J., Weaver, C.T., McCrory, M.A., van Ginkel, F.W., Reiman, R.M., Kearney, J.F., Marion, T.N., and Volanakis, J.E. (2003). Delayed lupus onset in (NZBxNZF)F1 mice expressing a human C-reactive protein transgene. Arthritis Rheum. 48, 1602–1611.10.1002/art.11026Search in Google Scholar PubMed

Szalai, A.J., McCrory, M.A., Xing, D., Hage, F.G., Miller, A., Oparil, S., Chen, Y.-F., Mazzone, M., Early, R., Henry, S.P., et al. (2014). Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models. Med. Inflamm. 2014, 353614.10.1155/2014/353614Search in Google Scholar PubMed PubMed Central

Tanigaki, K., Mineo, C., Yuhanna, I.S., Chambliss, K.L., Quon, M.J., Bonvini, E., and Shaul, P.W. (2007). C-reactive protein inhibits insulin activation of endothelial nitric oxide synthase via the immunoreceptor tyrosine-based inhibition motif of FcγRIIB and SHIP-1. Circ. Res. 104, 1275–1282.10.1161/CIRCRESAHA.108.192906Search in Google Scholar PubMed PubMed Central

Teupser, D., Weber, O., Rao, T.N., Sass, K., Thiery, J., and Fehling, H.J. (2011). No reduction of atherosclerosis in C-reactive protein (CRP)-deficient mice. J. Biol. Chem. 286, 6272–6279.10.1074/jbc.M110.161414Search in Google Scholar PubMed PubMed Central

Thiele, J.R., Habersberger, J., Braig, D., Schmidt, Y., Goerendt, K., Maurer, V., Bannasch, H., Scheichl, A., Woolard, K., von Dobschütz, E., et al. (2014). The dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful pro-inflammatory mechanisms and a new anti-inflammatory strategy. Circulation 130, 35–50.10.1161/CIRCULATIONAHA.113.007124Search in Google Scholar PubMed

Tilg, H., Vannier, E., Vachino, G., Dinarello, C.A., and Mier, J.W. (1993). Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1β synthesis by human peripheral blood mononuclear cells. J. Exp. Med. 178, 1629–1636.10.1084/jem.178.5.1629Search in Google Scholar PubMed PubMed Central

Tillett, W.S. and Francis, T. (1930). Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J. Exp. Med. 52, 561–571.10.1084/jem.52.4.561Search in Google Scholar PubMed PubMed Central

Torzewski, J., Torzewski, M., Bowyer, D.E., Frölich, M., Koenig, W., Waltenberger, J., Fitzsimmons, C., and Hornbach, V. (1998). C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler. Thromb. Vasc. Biol. 18, 1386–1392.10.1161/01.ATV.18.9.1386Search in Google Scholar

Torzewski, M., Rist, C., Mortensen, R.F., Zwaka, T.P., Bienek, M., Waltenberger, J., Koenig, W., Schmitz, G., Hombach, V., and Torzewski, J. (2000) C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler. Thromb. Vasc. Biol. 20, 2094–2099.Search in Google Scholar

Trion, A., de Maat, M.P., Jukema, J.W., van der Laarse, A., Maas, M.C., Offerman, E.H., Havekes, L.M., Szalai. A.J., Princen, H.M., and Emeis, J.J. (2005). No effect of C-reactive protein on early atherosclerosis development in apolipoprotein E*3-leiden/human C-reactive protein transgenic mice. Arterioscler. Thromb. Vasc. Biol. 25, 1635–1640.10.1161/01.ATV.0000171992.36710.1eSearch in Google Scholar PubMed

Tsimikas, S., Willerson, J.T., and Ridker, P.M. (2006). C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J. Am. Coll. Cardiol. 47, C19–C31.10.1016/j.jacc.2005.10.066Search in Google Scholar PubMed

van den Berg, C.W., Taylor, K.E., and Lang, D. (2004). C-reactive protein-induced in vivo vasorelaxation is an artefect caused by the presence of sodium azide in commercial preparations. Arterioscler. Thromb. Vasc. Biol. 24, 158–171.Search in Google Scholar

Venugopal, S.K., Devaraj, S., Yuhanna, I., Shaul, P., and Jialal, I. (2002). Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 106, 1439–1441.10.1161/01.CIR.0000033116.22237.F9Search in Google Scholar

Verma, S., Kuliszewski, M.A., Li, S.H., Szmitko, P.E., Zucco, L., Wang, C.H., Badiwala, M.V., Mickle, D.A., Weisel, R.D., Fedak, P.W., et al. (2004). C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and functionL further evidence of a mechanistic link between C-reactive protein and cardiovascular disease. Circulation 109, 2058–2067.10.1161/01.CIR.0000127577.63323.24Search in Google Scholar

Verma, S., Devaraj, S., and Jialal, I. (2006). C-reactive protein promotes atherothrombosis. Circulation 113, 2135–2151.Search in Google Scholar

Vigo, C. (1985). Effect of C-reactive protein on platelet-activating factor-induced platelet aggregation and membrane stabilization. J. Biol. Chem. 260, 3418–3422.10.1016/S0021-9258(19)83638-4Search in Google Scholar

Vigushin, D.M., Pepys, M.B., and Hawkins, P.N. (1993). Metabolic and scintigraphic studies of raioiodinated human C-reactive protein in health and disease. J. Clin. Invest. 91, 1351–1357.10.1172/JCI116336Search in Google Scholar PubMed PubMed Central

Vilahur, G., Hernández-Vera, R., Molins, B., Casani, L., Duran, X., Padró, T., and Badimon, L. (2009). Short-term myocardial ischemia induces cardiac modified C-reactive protein expression and proinflammatory gene (cyclo-oxygenase-2, monocyte chemoattractant protein-1, and tissue factor) upregulation in peripheral blood mononuclear cells. J. Thromb. Haemost. 7, 485–493.10.1111/j.1538-7836.2008.03244.xSearch in Google Scholar PubMed

Walsh, M.T., Divane, A., and Whitehead, A.S. (1996). Fine mapping of the human pentraxin gene region on chromosome 1q23. Immunogenetics 44, 62–69.10.1007/BF02602657Search in Google Scholar PubMed

Wang, H.W. and Sui, S.F. (2001). Dissociation and subunit rearrangement of membrane-bound human C-reactive proteins. Biochem. Biophys. Res. Commun. 288, 75–79.10.1006/bbrc.2001.5733Search in Google Scholar PubMed

Wang, M.S., Black, J.C., Knowles, M.K., and Reed, S.M. (2011a). C-reactive protein (CRP) aptamer binds to monomeric but not pentameric from of CRP. Anal. Bioanal. Chem. 401, 1309–1318.10.1007/s00216-011-5174-1Search in Google Scholar PubMed PubMed Central

Wang, M.-Y., Ji, S.-R., Bai, C.-J., El Kebir, D., Li, H.-Y., Shi, J.-M., Zhu, W., Costantino, S., Zhou, H.-H., Potempa, L.A., et al. (2011b). A redox switch in C-reactive protein modulates activation of endothelial cells. FASEB J. 25, 3186–3196.10.1096/fj.11-182741Search in Google Scholar PubMed

Wang, M.S., Messersmith R.E., and Reed, S.M. (2012). Membrane curvature recognition by C-reactive protein using lipoprotein mimics. Soft Matter 8, 7909–7918.10.1039/c2sm25779cSearch in Google Scholar

Wang, J., Tang, B., Liu, X., Wu, X., Wang, H., Xu, D., and Guo, Y. (2015). Increased monomeric CRP levels in acute myocardial infarction: a possible new and specific biomarker for diagnosis and severity assessment of disease. Atherosclerosis 239, 343–349.10.1016/j.atherosclerosis.2015.01.024Search in Google Scholar

Xia, D. and Samols, D. (1997). Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia. Proc. Natl. Acad. Sci. USA 94, 2575–2580.10.1073/pnas.94.6.2575Search in Google Scholar

Yasojima, K., Schwab, C., McGeer, E.G., and McGeer, P.L. (2001). Generation of C-reactive protein and complement components in atherosclerotic plaques. Am. J. Pathol. 158, 1039–1051.10.1016/S0002-9440(10)64051-5Search in Google Scholar

Ying, S.-C., Gewurz, H., Kinoshita, C.M., Potempa, L.A., and Siegel, J.N. (1989) Identification and partial characterization of multiple native and neoantigenic epitopes of human C-reactive protein. J. Immunol. 143, 221–228.Search in Google Scholar

Ying, S.-C., Shephard, E., de Beer, F.C., Siegel, J.N., Harris, D., Gewurz, B.E., Friedkin, M., and Gewurz, H. (1992). Localization of sequence-determined neoepitopes and neutrophil digestion fragments of C-reactive protein utilizing monoclonal antibodies and synthetic peptides. Mol. Immunol. 29, 677–687.10.1016/0161-5890(92)90205-CSearch in Google Scholar

Zhong, W., Zen, Q., Tebo, J., Schlottmann, K., Coggeshall, M., and Mortenson, R.F. (1998). Effect of human C-reactive protein on chemokine and chemotactic factor-induced neutrophil chemotaxis and signaling. J. Immunol. 161, 2533–2540.Search in Google Scholar

Zhou, P., Thomassen, M.J., Pettay, J., Deodhar, S.D., and Barna, B.P. (1995). Human monocytes produce monocyte chemoattractant protein 1 (MCP-1) in response to a synthetic peptide derived from C-reactive protein. Clin. Immunol. Immunopathol. 74, 84–88.10.1006/clin.1995.1012Search in Google Scholar PubMed

Zouki, C., Beauchamp, M., Baron, C., and Filep, J.G. (1997). Prevention of in vitro neutrophil adhesion to endothelial cells through shedding of L-selectin by C-reactive protein and peptides derived from C-reactive protein. J. Clin. Invest. 100, 522–529.10.1172/JCI119561Search in Google Scholar PubMed PubMed Central

Zouki, C., Haas, B., Chan, J.S.D., Potempa, L.A., and Filep, J.G. (2001). Loss of pentameric symmetry of C-reactive protein is associated with promotion of neutrophil-endothelial cell adhesion. J. Immunol. 167, 5355–5361.10.4049/jimmunol.167.9.5355Search in Google Scholar PubMed

Zwaka, T.P., Hombach, V., and Torzewski, J. (2001). C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 103, 1194–1197.10.1161/01.CIR.103.9.1194Search in Google Scholar PubMed

Received: 2015-3-30
Accepted: 2015-5-29
Published Online: 2015-6-2
Published in Print: 2015-11-1

©2015 by De Gruyter

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