Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter September 21, 2011

Effect of interferon-γ, interleukin-10, lipopolysaccharide and tumor necrosis factor-α on chitotriosidase synthesis in human macrophages

  • Michelino Di Rosa , Maria Musumeci , Anna Scuto , Salvatore Musumeci and Lucia Malaguarnera


Human chitotriosidase is a chitinolytic enzyme and mainly produced by activated macrophages. Recently, we observed that prolactin, which is structurally related to several cytokines and is involved in regulating monocyte/macrophage functions, upregulates chitotriosidase gene expression in human macrophages, suggesting that chitotriosidase is not only a biochemical marker of macrophage activation in lysosomal diseases and hematological disorders, but also may reflect induction of an immunological response. To confirm this hypothesis we evaluated by quantitative real-time PCR the mRNA chitotriosidase levels in human monocytes/macrophages following treatment with pro-inflammatory stimuli such as interferon-γ, tumor necrosis factor-α, lipopolysaccharide, and interleukin-10, an anti-inflammatory cytokine. Stimulation of macrophages with interferon-γ, tumor necrosis factor-α and lipopolysaccharide resulted in increased levels of chitotriosidase mRNA, as well as chitotriosidase activity, whereas interleukin-10 decreased chitotriosidase synthesis. This finding is consistent with the hypothesis that the production of chitotriosidase by macrophages could have biological relevance in the immune response.

Corresponding author: Lucia Malaguarnera, E. De Amicis, 24, 95039 Trecastagni, Catania, Italy Fax: +39-095-7807843, E-mail:


1 Fusetti F, von Moeller H, Houston D, Rozeboom HJ, Dijkstra BW, Boot RG, et al. Structure of human chitotriosidase. Implications for specific inhibitor design and function of mammalian chitinase-like lectins. J Biol Chem 2002; 277: 25537–44. 10.1074/jbc.M201636200Search in Google Scholar

2 Debono M, Gordee RS. Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 1994; 48: 471–7. 10.1146/annurev.mi.48.100194.002351Search in Google Scholar

3 Araujo AC, Souto-Padron T, de Souza W. Cytochemical localization of carbohydrate residues in microfilariae of Wuchereria bancrofti and Brugia malayi. J Histochem Cytochem 1993; 41: 571–8. 10.1177/41.4.8450196Search in Google Scholar

4 Shahabuddin M, Kaslow DC. Plasmodium: parasite chitinase and its role in malaria transmission. Exp Parasitol 1994; 79: 85–8. 10.1006/expr.1994.1066Search in Google Scholar

5 Boot RG, Renkema GH, Strijland A, van Zonneveld AJ, Aerts JM. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem 1995; 270: 26252–6. 10.1074/jbc.270.44.26252Search in Google Scholar

6 Henrissat B, Bairoch A. New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 1993; 293: 781–8. 10.1042/bj2930781Search in Google Scholar

7 Eiberg H, Den Tandt WR. Assignment of human plasma methylumbelliferyl-tetra-N-acetylchitotetraoside hydrolase or chitinase to chromosome 1q by a linkage study. Hum Genet 1997; 101: 205–7. 10.1007/s004390050615Search in Google Scholar

8 Renkema GH, Boot RG, Strijland A, Donker-Koopman WE, van den Berg M, Muijsers AO, et al. Synthesis, sorting and processing into distinct isoforms of humanmacrophage chitotriosidase. Eur J Biochem 1997; 244: 279–85. 10.1111/j.1432-1033.1997.00279.xSearch in Google Scholar

9 Boussac M, Garin J. Calcium-dependent secretion in human neutrophils: a proteomic approach. Electrophoresis 2000; 21: 665–72. 10.1002/(SICI)1522-2683(20000201)21:3<665::AID-ELPS665>3.0.CO;2-USearch in Google Scholar

10 Hollak CE, van Weely S, van Oers MHJ, Aerts JM. Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 1994; 93: 1288–92. 10.1172/JCI117084Search in Google Scholar

11 Boot RG, Blommaart EF, Swart E, Ghauharali-van der Vlugt K, Bijl N, Moe C, et al. Identification of a novel acidic mammalian chitinase distinct from chitotriosidase. J Biol Chem 2001; 276: 6770–8. 10.1074/jbc.M009886200Search in Google Scholar

12 Barone R, Simporè J, Malaguarnera L, Pignatelli S, Musumeci S. Plasma chitotriosidase activity in acute Plasmodium falciparum malaria. Clin Chim Acta 2003; 331: 79–85. 10.1016/S0009-8981(03)00089-5Search in Google Scholar

13 Barone R, Di Gregorio F, Romeo MA, Schilirò G, Pavone L. Plasma chitotriosidase activity in patients with β-thalassemia. Blood Cell Mol Dis 1999; 15: 1–8. 10.1006/bcmd.1999.0221Search in Google Scholar

14 Malaguarnera L, Musumeci M, Licata F, Di Rosa M, Messina A, Musumeci S. Prolactin induces chitotriosidase gene expression in human monocyte-derived macrophages. Immunol Lett 2004; 94: 57–63. 10.1016/j.imlet.2004.03.009Search in Google Scholar

15 Howard M, O'Garra A. Biological properties of interleukin 10. Immunol Today 1992; 13: 198–200. 10.1016/0167-5699(92)90153-XSearch in Google Scholar

16 Lauw FN, te Velde AA, Dekkers PE, Speelman P, Aerts JM, Hack CE, et al. Activation of mononuclear cells by interleukin-12: an in vivo study in chimpanzees. J Clin Immunol 1999; 19: 231–2. 10.1023/A:1020520130792Search in Google Scholar

17 Choi EH, Zimmerman PA, Foster CB, Zhu S, Kumaraswami V, Nutman TB, et al. Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India. Genes Immun 2001; 2: 248–53. 10.1038/sj.gene.6363767Search in Google Scholar PubMed

18 Malaguarnera L, Simporè J, Prodi DA, Angius A, Sassu A, Persico I, et al. A 24-bp duplication in exon 10 of human chitotriosidase gene from the sub-Saharan to the Mediterranean area: role of parasitic diseases and environmental conditions. Genes Immun 2003; 4: 570–4. 10.1038/sj.gene.6364025Search in Google Scholar PubMed

Received: 2005-1-25
Accepted: 2005-3-14
Published Online: 2011-9-21
Published in Print: 2005-5-1

© by Walter de Gruyter Berlin New York

Downloaded on 6.2.2023 from
Scroll Up Arrow