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Licensed Unlicensed Requires Authentication Published by De Gruyter June 30, 2018

The function of sphingomyelinases in mycobacterial infections

Yuqing Wu , Erich Gulbins and Heike Grassmé EMAIL logo
From the journal Biological Chemistry

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the deadliest and most important infectious diseases worldwide. The sphingomyelinase/ceramide system, which has been shown several times to be a crucial factor in the internalization, processing and killing of diverse pathogens, also modulates the pro-inflammatory response and the state of mycobacteria in macrophages. Both acid and neutral sphingomyelinases are important in this activity. However, studies of the role of sphingomyelinases in TB are still at an early stage.

Award Identifier / Grant number: GR 1697/2-1

Funding statement: Deutsche Forschungsgemeinschaft, Funder Id: 10.13039/501100001659, Grant Number: GR 1697/2-1.

References

Anes, E., Kühnel, M.P., Bos, E., Moniz-Péreira, J., Habermann, A., and Griffiths, G. (2003). Selected lipids activate phagosome actin assembly and maturation resulting in killing of pathogenic mycobacteria. Nat. Cell Biol. 5, 793–802.10.1038/ncb1036Search in Google Scholar

Avota, E., Gulbins, E., and Schneider-Schaulies, S. (2011). DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells. PLoS Pathog. 7, e1001290.10.1371/journal.ppat.1001290Search in Google Scholar

Becker, K.A., Henry, B., Ziobro, R., Tümmler, B., Gulbins, E., and Grassmé, H. (2012). Role of CD95 in pulmonary inflammation and infection in cystic fibrosis. J. Mol. Med. 90, 1011–1023.10.1007/s00109-012-0867-2Search in Google Scholar

Beckmann, N., Sharma, D., Gulbins, E., Becker, K.A., and Edelmann, B. (2014). Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. Front. Physiol. 5, 331.10.3389/fphys.2014.00331Search in Google Scholar

Beiguelman, B. (1967). Leprosy and genetics. A review of past research with remarks concerning future investigations. Bull. World Health Org. 37, 461–476.Search in Google Scholar

Carpinteiro, A., Becker, K.A., Japtok, L., Hessler, G., Keitsch, S., Požgajovà, M., Schmid, K.W., Adams, C., Müller, S., Kleuser, B., et al. (2015). Regulation of hematogenous tumor metastasis by acid sphingomyelinase. EMBO Mol. Med. 7, 714–734.10.15252/emmm.201404571Search in Google Scholar

Cremesti, A.E., Goni, F.M., and Kolesnick, R. (2002). Role of sphingomyelinase and ceramide in modulating rafts: do biophysical properties determine biologic outcome? FEBS Lett. 531, 47–53.10.1016/S0014-5793(02)03489-0Search in Google Scholar

Cronan, M.R., Beerman, R.W., Rosenberg, A.F., Saelens, J.W., Johnson, M.G., Öhlers, S.H., Sisk, D.M., Jurcic Smith, K.L., Medvitz, N.A., Miller, S.E., et al. (2016). Macrophage epithelial reprogramming underlies mycobacterial granuloma formation and promotes infection. Immunity 45, 861–876.10.1016/j.immuni.2016.09.014Search in Google Scholar

da Veiga Pereira, L., Desnick, R.J., Adler, D.A., Disteche, C.M., and Schuchman, E.H. (1991). Regional assignment of the human acid sphingomyelinase gene (Smpd1) by PCR analysis of somatic cell hybrids and in situ hybridization to 11p15.1-p15.4. Genomics 9, 229–234.10.1016/0888-7543(91)90246-BSearch in Google Scholar

Davis, J.M. and Ramakrishnan, L. (2009). The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell 136, 37–49.10.1016/j.cell.2008.11.014Search in Google Scholar PubMed PubMed Central

Dheda, K., Schwander, S.K., Zhu, B., van Zyl-Smit, R.N., and Zhang, Y. (2010). The immunology of tuberculosis: from bench to bedside. Respirology 15, 433–450.10.1111/j.1440-1843.2010.01739.xSearch in Google Scholar PubMed PubMed Central

Dreschers, S., Franz, P., Dumitru, C., Wilker, B., Jahnke, K., and Gulbins, E. (2007). Infections with human rhinovirus induce the formation of distinct functional membrane domains. Cell. Physiol. Biochem. 20, 241–254.10.1159/000104170Search in Google Scholar

Duan, R.D. (2006). Alkaline sphingomyelinase: an old enzyme with novel implications. Biochim. Biophys. Acta 1761, 281–291.10.1016/j.bbalip.2006.03.007Search in Google Scholar

Esen, M., Schreiner, B., Jendrossek, V., Lang, F., Fassbender, K., Grassmé, H., and Gulbins, E. (2001). Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells. Apoptosis 6, 431–439.10.1023/A:1012445925628Search in Google Scholar

Falcone, S., Perrotta, C., De Palma, C., Pisconti, A., Sciorati, C., Capobianco, A., Rovere-Querini, P., Manfredi, A.A., and Clementi, E. (2004). Activation of acid sphingomyelinase and its inhibition by the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway: key events in Escherichia coli-elicited apoptosis of dendritic cells. J. Immunol. 173, 4452–4463.10.4049/jimmunol.173.7.4452Search in Google Scholar

Faulstich, M., Hagen, F., Avota, E., Kozjak-Pavlovic, V., Winkler, A.C., Xian, Y., Schneider-Schaulies, S., and Rudel, T. (2015). Neutral sphingomyelinase 2 is a key factor for PorB-dependent invasion of Neisseria gonorrhoeae. Cell. Microbiol. 17, 241–253.10.1111/cmi.12361Search in Google Scholar

Gassert, E., Avota, E., Harms, H., Krohne, G., Gulbins, E., and Schneider-Schaulies, S. (2009). Induction of membrane ceramides: a novel strategy to interfere with T lymphocyte cytoskeletal reorganisation in viral immunosuppression. PLoS Pathog. 5, e1000623.10.1371/journal.ppat.1000623Search in Google Scholar

Gatt, S. (1963). Enzymic hydrolysis and synthesis of ceramides. J. Biol. Chem. 238, 3131–3133.10.1016/S0021-9258(18)51879-2Search in Google Scholar

Goñi, F.M. and Alonso, A. (2002). Sphingomyelinases: enzymology and membrane activity. FEBS Lett. 531, 38–46.10.1016/S0014-5793(02)03482-8Search in Google Scholar

Gorelik, A., Illes, K., Heinz, L.X., Superti-Furga, G., and Nagar, B. (2016). Crystal structure of mammalian acid sphingomyelinase. Nat. Commun. 7, 12196.10.1038/ncomms12196Search in Google Scholar

Grassmé, H., Gulbins, E., Brenner, B., Ferlinz, K., Sandhoff, K., Harzer, K., Lang, F., and Meyer, T.F. (1997). Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells. Cell 91, 605–615.10.1016/S0092-8674(00)80448-1Search in Google Scholar

Grassmé, H., Kirschnek, S., Riethmüller, J., Riehle, A., von Kürthy, G., Lang, F., Weller, M., and Gulbins, E. (2000). CD95/CD95 ligand interactions on epithelial cells in host defense to Pseudomonas aeruginosa. Science 290, 527–530.10.1126/science.290.5491.527Search in Google Scholar PubMed

Grassmé, H., Jekle, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E. (2001). CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276, 20589–20596.10.1074/jbc.M101207200Search in Google Scholar PubMed

Grassmé, H., Jendrossek, V., Riehle, A., von Kürthy, G., Berger, J., Schwarz, H., Weller, M., Kolesnick, R., and Gulbins, E. (2003). Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat. Med. 9, 322–330.10.1038/nm823Search in Google Scholar PubMed

Grassmé, H., Riehle, A., Wilker, B., and Gulbins, E. (2005). Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms. J. Biol. Chem. 280, 26256–26262.10.1074/jbc.M500835200Search in Google Scholar PubMed

Grassmé, H., Riethmüller, J., and Gulbins, E. (2007). Biological aspects of ceramide-enriched membrane domains. Prog. Lipid Res. 46, 161–170.10.1016/j.plipres.2007.03.002Search in Google Scholar PubMed

Grassmé, H., Henry, B., Ziobro, R., Becker, K.A., Riethmüller, J., Gardner, A., Seitz, A.P., Steinmann, J., Lang, S., Ward, C., et al. (2017). β1-Integrin accumulates in cystic fibrosis luminal airway epithelial membranes and decreases sphingosine, promoting bacterial infections. Cell Host Microbe 21, 707–718.10.1016/j.chom.2017.05.001Search in Google Scholar PubMed PubMed Central

Gulbins, E. and Li, P.L. (2006). Physiological and pathophysiological aspects of ceramide. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R11–R26.10.1152/ajpregu.00416.2005Search in Google Scholar PubMed

Gutierrez, M.G., Mishra, B.B., Jordao, L., Elliott, E., Anes, E., and Griffiths, G. (2008). NF-kappa B activation controls phagolysosome fusion-mediated killing of mycobacteria by macrophages. J. Immunol. 181, 2651–2663.10.4049/jimmunol.181.4.2651Search in Google Scholar PubMed

Haimovitz-Friedman, A., Kan, C.C., Ehleiter, D., Persaud, R.S, McLoughlin, M., Fuks, Z., and Kolesnick, R.N. (1994). Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J. Exp. Med. 180, 525–535.10.1084/jem.180.2.525Search in Google Scholar PubMed PubMed Central

Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell. Biol. 9, 139–150.10.1038/nrm2329Search in Google Scholar PubMed

Hauck, C.R., Grassmé, H., Bock, J., Jendrossek, V., Ferlinz, K., Meyer, T.F., and Gulbins, E. (2000). Acid sphingomyelinase is involved in CEACAM receptor-mediated phagocytosis of Neisseria gonorrhoeae. FEBS Lett. 478, 260–266.10.1016/S0014-5793(00)01851-2Search in Google Scholar

Hedlund, M., Duan, R.D., Nilsson, A., and Svanborg, C. (1998). Sphingomyelin, glycosphingolipids and ceramide signalling in cells exposed to P-fimbriated Escherichia coli. Mol. Microbiol. 29, 1297–1306.10.1046/j.1365-2958.1998.01017.xSearch in Google Scholar PubMed

Hofmann, K., Tomiuk, S., Wolff, G., and Stoffel, W. (2000). Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc. Natl. Acad. Sci. USA 97, 5895–5900.10.1073/pnas.97.11.5895Search in Google Scholar PubMed PubMed Central

Hwang, J.A., Kim, S., Jo, K.W., and Shim, T.S. (2017). Natural history of Mycobacterium avium complex lung disease in untreated patients with stable course. Eur. Resp. J. 49.Search in Google Scholar

Jenkins, R.W., Canals, D., and Hannun, Y.A. (2009). Roles and regulation of secretory and lysosomal acid sphingomyelinase. Cell. Signal. 21, 836–846.10.1016/j.cellsig.2009.01.026Search in Google Scholar PubMed PubMed Central

Koch, R. (1882). The etiology of tuberculosis. Berl. Klin. Wochenschr. 15, 221–230 [in German].10.1093/clinids/4.6.1270Search in Google Scholar

Kolesnick, R.N., Haimovitz-Friedman, A., and Fuks, Z. (1994). The sphingomyelin signal transduction pathway mediates apoptosis for tumor necrosis factor, Fas, and ionizing radiation. Biochem. Cell. Biol. 72, 471–474.10.1139/o94-063Search in Google Scholar PubMed

Kozinn, W.P., Damsker, B., and Bottone, E.J. (1980). Mycobacterium avium complex: significance of isolation from bone marrow culture. J. Clin. Microbiol. 11, 245–248.10.1128/jcm.11.3.245-248.1980Search in Google Scholar PubMed PubMed Central

Li, C., Peng, H., Japtok, L., Seitz, A., Riehle, A., Wilker, B., Soddemann, M., Kleuser, B., Edwards, M., Lammas, D., et al. (2016). Inhibition of neutral sphingomyelinase protects mice against systemic tuberculosis. Front. Biosci. (Elite Ed.) 8, 311–325.Search in Google Scholar

Li, C., Wu, Y., Riehle, A., Orian-Rousseau, V., Zhang, Y., Gulbins, E., and Grassmé, H. (2017). Regulation of Staphylococcus aureus infection of macrophages by CD44, reactive oxygen species, and acid sphingomyelinase. Antioxid. Redox Signal. 29.10.1089/ars.2017.6994Search in Google Scholar PubMed

Luciani, A., Villella, V.R., Esposito, S., Brunetti-Pierri, N., Medina, D., Settembre, C., Gavina, M., Pulze, L., Giardino, I., Pettoello-Mantovani, M., et al. (2010). Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat. Cell Biol. 12, 863–875.10.1038/ncb2090Search in Google Scholar PubMed

Luisoni, S., Suomalainen, M., Boucke, K., Tanner, L.B., Wenk, M.R., Guan, X.L., Grzybek, M., Coskun, U., and Greber, U.F. (2015). Co-option of membrane wounding enables virus penetration into cells. Cell Host Microbe. 18, 75–85.10.1016/j.chom.2015.06.006Search in Google Scholar PubMed

Ma, J., Gulbins, E., Edwards, M.J., Caldwell, C.C., Fraunholz, M., and Becker, K.A. (2017). Staphylococcus aureus α-toxin induces inflammatory cytokines via lysosomal acid sphingomyelinase and ceramides. Cell. Physiol. Biochem. 43, 2170–2184.10.1159/000484296Search in Google Scholar PubMed

Majumder, S., Dey, R., Bhattacharjee, S., Rub, A., Gupta, G., Bhattacharyya Majumdar, S., Saha, B., and Majumdar, S. (2012). Leishmania-induced biphasic ceramide generation in macrophages is crucial for uptake and survival of the parasite. J. Infect. Dis. 205, 1607–1616.10.1093/infdis/jis229Search in Google Scholar PubMed

McCollister, B.D., Myers, J.T., Jones-Carson, J., Völker, D.R., and Vázquez-Torres, A. (2007). Constitutive acid sphingomyelinase enhances early and late macrophage killing of Salmonella enterica serovar Typhimurium. Infect. Immun. 75, 5346–5352.10.1128/IAI.00689-07Search in Google Scholar PubMed PubMed Central

Miller, M.E., Adhikary, S., Kolokoltsov, A.A., and Davey, R.A. (2012). Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J. Virol. 86, 7473–7483.10.1128/JVI.00136-12Search in Google Scholar PubMed PubMed Central

Münzner, P., Bachmann, V., Zimmermann, W., Hentschel, J., and Hauck, C.R. (2010). Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation. Science 329, 1197–1201.10.1126/science.1190892Search in Google Scholar PubMed

Nakatsuji, T., Tang, D.C., Zhang, L., Gallo, R.L., and Huang, C.M. (2011). Propionibacterium acnes CAMP factor and host acid sphingomyelinase contribute to bacterial virulence: potential targets for inflammatory acne treatment. PLoS One 6, e14797.10.1371/journal.pone.0014797Search in Google Scholar PubMed PubMed Central

Nathan, C. and Shiloh, M.U. (2000). Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA 97, 8841–8848.10.1073/pnas.97.16.8841Search in Google Scholar PubMed PubMed Central

Nunes-Alves, C., Booty, M.G., Carpenter, S.M., Jayaraman, P., Rothchild, A.C., and Behar, S. M. (2014). In search of a new paradigm for protective immunity to TB. Nat. Rev. Microbiol. 12, 289–299.10.1038/nrmicro3230Search in Google Scholar PubMed PubMed Central

Peng, H., Li, C., Kadow, S., Henry, B.D., Steinmann, J., Becker, K.A., Riehle, A., Beckmann, N., Wilker, B., Li, P.L., et al. (2015). Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis. J. Mol. Med. 93, 675–689.10.1007/s00109-014-1246-ySearch in Google Scholar PubMed PubMed Central

Peyron, P., Vaubourgeix, J., Poquet, Y., Levillain, F., Botanch, C., Bardou, F., Daffé, M., Emile, J.F., Marchou, B., Cardona, P.J., et al. (2008). Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog. 4, e1000204.10.1371/journal.ppat.1000204Search in Google Scholar PubMed PubMed Central

Qrafli, M., Asekkaj, I., Bourkadi, J.E., El Aoud, R., and Sadki, K. (2017). New variant identified in major susceptibility locus to tuberculosis on chromosomal region 8Q12-q13 in Moroccan population: a case control study. BMC Infect. Dis. 7, 712.10.1186/s12879-017-2807-9Search in Google Scholar

Reibel, F., Cambau, E., and Aubry, A. (2015) Update on the epidemiology, diagnosis, and treatment of leprosy. Med. Mal. Infect. 45, 383–393.10.1016/j.medmal.2015.09.002Search in Google Scholar

Roca, F.J. and Ramakrishnan, L. (2013). TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell 153, 521–534.10.1016/j.cell.2013.03.022Search in Google Scholar

Russell, D.G. (2007). Who puts the tubercle in tuberculosis? Nat. Rev. Microbiol. 5, 39–47.10.1038/nrmicro1538Search in Google Scholar

Schissel, S.L., Keesler, G.A., Schuchman, E.H., Williams, K.J., and Tabas, I. (1998). The cellular trafficking and zinc dependence of secretory and lysosomal sphingomyelinase, two products of the acid sphingomyelinase gene. J. Biol. Chem. 273, 18250–18259.10.1074/jbc.273.29.18250Search in Google Scholar

Schramm, M., Herz, J., Haas, A., Krönke, M., and Utermöhlen, O. (2008). Acid sphingomyelinase is required for efficient phago-lysosomal fusion. Cell. Microbiol. 10, 1839–1853.10.1111/j.1462-5822.2008.01169.xSearch in Google Scholar

Schuchman, E.H., Levran, O., Pereira, L.V., and Desnick, R.J. (1992). Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (Smpd1). Genomics 12, 197–205.10.1016/0888-7543(92)90366-ZSearch in Google Scholar

Schütze, S., Potthoff, K., Machleidt, T., Berkovic, D., Wiegmann, K., and Krönke, M. (1992). TNF activates NF-κB by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell 71, 765–776.10.1016/0092-8674(92)90553-OSearch in Google Scholar

Schwandner, R., Wiegmann, K., Bernardo, K., Kreder, D., and Kronke, M. (1998). TNF receptor death domain-associated proteins TRADD and FADD signal activation of acid sphingomyelinase. J. Biol. Chem. 273, 5916–5922.10.1074/jbc.273.10.5916Search in Google Scholar PubMed

Ségui, B., Cuvillier, O., Adam-Klages, S., Garcia, V., Malagarie-Cazenave, S., Léveque, S., Caspar-Bauguil, S., Coudert, J., Salvayre, R., Krönke, M., et al. (2001). Involvement of FAN in TNF-induced apoptosis. J. Clin. Invest. 108, 143–151.10.1172/JCI11498Search in Google Scholar PubMed PubMed Central

Shamseddine, A.A., Airola, M.V., and Hannun, Y.A. (2015). Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes. Adv. Biol. Regul. 57, 24–41.10.1016/j.jbior.2014.10.002Search in Google Scholar

Simonis, A., Hebling, S., Gulbins, E., Schneider-Schaulies, S., and Schubert-Unkmeir, A. (2014). Differential activation of acid sphingomyelinase and ceramide release determines invasiveness of Neisseria meningitidis into brain endothelial cells. PLoS Pathog. 10, e1004160.10.1371/journal.ppat.1004160Search in Google Scholar

Takahashi, T., Suchi, M., Desnick, R.J, Takada, G., and Schuchman, E.H. (1992). Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms. J. Biol. Chem. 267, 12552–12558.10.1016/S0021-9258(18)42312-5Search in Google Scholar

Tani, M. and Hannun, Y.A. (2007). Neutral sphingomyelinase 2 is palmitoylated on multiple cysteine residues. Role of palmitoylation in subcellular localization. J. Biol. Chem. 282, 10047–10056.10.1074/jbc.M611249200Search in Google Scholar PubMed

Teichgräber, V., Ulrich, M., Endlich, N., Riethmüller, J., Wilker, B., De Oliveira-Munding, C.C., van Heeckeren, A.M., Barr, M.L., von Kürthy, G., Schmid, K.W., et al. (2008). Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med. 14, 382–391.10.1038/nm1748Search in Google Scholar PubMed

Tonnetti, L., Verí, M.C., Bonvini, E., and D’Adamio, L.A. (1999). Role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction. J. Exp. Med. 189, 1581–1589.10.1084/jem.189.10.1581Search in Google Scholar PubMed PubMed Central

Utermöhlen, O., Karow, U., Löhler, J., and Krönke, M. (2003). Severe impairment in early host defense against Listeria monocytogenes in mice deficient in acid sphingomyelinase. J. Immunol. 170, 2621–2628.10.4049/jimmunol.170.5.2621Search in Google Scholar PubMed

Utermöhlen, O., Herz, J., Schramm, M., and Krönke, M. (2008). Fusogenicity of membranes: the impact of acid sphingomyelinase on innate immune responses. Immunobiology 213, 307–314.10.1016/j.imbio.2007.10.016Search in Google Scholar PubMed

Vázquez, C.L., Rodgers, A., Herbst, S., Coade, S., Gronow, A., Guzman, C.A., Wilson, M.S., Kanzaki, M., Nykjaer, A., and Gutierrez, M.G. (2016). The proneurotrophin receptor sortilin is required for Mycobacterium tuberculosis control by macrophages. Sci. Rep. 6, 29332.10.1038/srep29332Search in Google Scholar PubMed PubMed Central

Wähe, A., Kasmapour, B., Schmaderer, C., Liebl, D., Sandhoff, K., Nykjaer, A., Griffiths, G., and Gutiérrez, M.G. (2010). Golgi-to-phagosome transport of acid sphingomyelinase and prosaposin is mediated by sortilin. J. Cell Sci. 123, 2502–2511.10.1242/jcs.067686Search in Google Scholar PubMed

World Health Organization. (2017). Global tuberculosis report 2017. http://www.who.int/tb/publications/global_report/en/. Accessed May 12, 2018.Search in Google Scholar

Yu, H., Zeidan, Y.H., Wu, B.X., Jenkins, R.W., Flotte, T.R., Hannun, Y.A., and Virella-Lowell, I. (2009). Defective acid sphingomyelinase pathway with Pseudomonas aeruginosa infection in cystic fibrosis. Am. J. Respir. Cell Mol. Biol. 41, 367–375.10.1165/rcmb.2008-0295OCSearch in Google Scholar PubMed PubMed Central

Zhang, Y., Li, X., Carpinteiro, A., and Gulbins, E. (2008). Acid sphingomyelinase amplifies redox signaling in Pseudomonas aeruginosa-induced macrophage apoptosis. J. Immun. 181, 4247–4254.10.4049/jimmunol.181.6.4247Search in Google Scholar PubMed

Zhang, Y., Li, X., Becker, K.A., and Gulbins, E. (2009). Ceramide-enriched membrane domains – structure and function. Biochim. Biophys. Acta 1788, 178–183.10.1016/j.bbamem.2008.07.030Search in Google Scholar PubMed

Zhang, Y., Li, X., Grassmé, H., Döring, G., and Gulbins, E. (2010). Alterations in ceramide concentration and pH determine the release of reactive oxygen species by Cftr-deficient macrophages on infection. J. Immunol. 184, 5104–5111.10.4049/jimmunol.0902851Search in Google Scholar PubMed

Received: 2018-03-09
Accepted: 2018-06-06
Published Online: 2018-06-30
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

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