Cell Biochemistry and Biophysics

, Volume 66, Issue 2, pp 239–247 | Cite as

Modulation of Chitotriosidase During Macrophage Differentiation

  • Michelino Di Rosa
  • Giulia Malaguarnera
  • Corinne De Gregorio
  • Fabio D’Amico
  • Maria Clorinda Mazzarino
  • Lucia Malaguarnera
Original Paper

Abstract

Macrophages as a principal component of immune system play an important role in the initiation, modulation, and final activation of the immune response against pathogens. Upon stimulation with different cytokines, macrophages can undergo classical or alternative activation to become M1 or M2 macrophages, which have different functions during infections. Although chitotriosidase is widely accepted as a marker of activated macrophages and is thought to participate in innate immunity, particularly in defense mechanisms against chitin containing pathogens, little is known about its expression during macrophages full maturation and polarization. In this study we analyzed CHIT-1 modulation during monocyte-to-macrophage maturation and during their polarization. The levels of CHIT-1 expression was investigated in human monocytes obtained from buffy coat of healthy volunteers, polarized to classically activated macrophages (or M1), whose prototypical activating stimuli are interferon-γ and lipopolysaccharide, and alternatively activated macrophages (or M2) obtained by interleukin-4 exposure by real-time PCR and by Western blot analysis. During monocyte–macrophage differentiation both protein synthesis and mRNA analysis showed that CHIT-1 rises significantly and is modulated in M1 and M2 macrophages.Our results demonstrated that variations of CHIT-1 production are strikingly associated with macrophages polarization, indicating a different rule of this enzyme in the specialized macrophages.

Keywords

Chitotriosidase Monocyte Macrophages M1 M2 Immuno-response 

References

  1. 1.
    Ross, R., Ross, X. L., Ghadially, H., Lahr, T., Schwing, J., Knop, J., et al. (1999). Mouse langerhans cells differentially express an activated T cell attracting CC chemokine. Journal of Investigative Dermatology, 113, 991–998.PubMedCrossRefGoogle Scholar
  2. 2.
    Martinez, F. O., Sica, A., Mantovani, A., & Locati, M. (2008). Macrophage activation and polarization. Frontiers in Bioscience, 13, 453–461.PubMedCrossRefGoogle Scholar
  3. 3.
    van Eijk, M., van Roomen, C. P., Renkema, G. H., Bussink, A. P., Andrews, L., Blommaart, E. F., et al. (2005). Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity. International Immunology, 17, 1505–1512.PubMedCrossRefGoogle Scholar
  4. 4.
    Malaguarnera, L. (2006). Chitotriosidase: The yin and yang. Cellular and Molecular Life Sciences, 63, 3018–3029.PubMedCrossRefGoogle Scholar
  5. 5.
    van Eijk, M., Voorn-Brouwer, T., Scheij, S. S., Verhoeven, A. J., Boot, R. G., & Aerts, J. M. (2010). Curdlan-mediated regulation of human phagocyte-specific chitotriosidase. FEBS Letters, 584, 3165–3169.PubMedCrossRefGoogle Scholar
  6. 6.
    Bussink, A. P., van Eijk, M., Renkema, G. H., Aerts, J. M., & Boot, R. G. (2006). The biology of the Gaucher cell: The cradle of human chitinases. International Review of Cytology, 252, 71–128.PubMedCrossRefGoogle Scholar
  7. 7.
    Boven, L. A., van Meurs, M., Boot, R. G., Mehta, A., Boon, L., Aerts, J. M., et al. (2004). Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages. American Journal of Clinical Pathology, 122, 359–369.PubMedCrossRefGoogle Scholar
  8. 8.
    Barone, R., Bertrand, G., Simporè, J., Malaguarnera, M., & Musumeci, S. (2001). Plasma chitotriosidase activity in beta-thalassemia major: A comparative study between Sicilian and Sardinian patients. Clinica Chimica Acta, 306, 91–96.CrossRefGoogle Scholar
  9. 9.
    Bargagli, E., Maggiorelli, C., & Rottoli, P. (2008). Human chitotriosidase: A potential new marker of sarcoidosis severity. Respiration, 76, 234–238.PubMedCrossRefGoogle Scholar
  10. 10.
    Comabella, M., Domínguez, C., Rio, J., Martín-Gallán, P., Vilches, A., Vilarrasa, N., et al. (2009). Plasma chitotriosidase activity in multiple sclerosis. Clinical Immunology, 131, 216–222.PubMedCrossRefGoogle Scholar
  11. 11.
    Malaguarnera, L., Simporè, J., Prodi, D. A., Angius, A., Sassu, A., Persico, I., et al. (2003). 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 and Immunity, 4, 570–574.PubMedCrossRefGoogle Scholar
  12. 12.
    Artieda, M., Cenarro, A., Gañán, A., Lukic, A., Moreno, E., Puzo, J., et al. (2007). Serum chitotriosidase activity, a marker of activated macrophages, predicts new cardiovascular events independently of C-reactive protein. Cardiology, 108, 297–306.PubMedCrossRefGoogle Scholar
  13. 13.
    Palasik, W., Fiszer, U., Lechowicz, W., Czartoryska, B., Krzesiewicz, M., & Lugowska, A. (2005). Assessment of relations between clinical outcome of ischemic stroke and activity of inflammatory processes in the acute phase based on examination of selected parameters. European Neurology, 53, 188–193.PubMedCrossRefGoogle Scholar
  14. 14.
    Di Rosa, M., Dell’Ombra, N., Zambito, A. M., Malaguarnera, M., Nicoletti, F., & Malaguarnera, L. (2006). Chitotriosidase and inflammatory mediator levels in Alzheimer’s disease and cerebrovascular dementia. European Journal of Neuroscience, 23, 2648–2656.PubMedCrossRefGoogle Scholar
  15. 15.
    Malaguarnera, L., Di Rosa, M., Zambito, A. M., dell’Ombra, N., Di Marco, R., & Malaguarnera, M. (2006). Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution. American Journal of Gastroenterology, 101, 2060–2069.PubMedCrossRefGoogle Scholar
  16. 16.
    Malaguarnera, L., Di Rosa, M., Zambito, A. M., dell’Ombra, N., Nicoletti, F., & Malaguarnera, M. (2006). Chitotriosidase gene expression in Kupffer cells from patients with non-alcoholic fatty liver disease. Gut, 55, 1313–1320.PubMedCrossRefGoogle Scholar
  17. 17.
    Kzhyshkowska, J., Gratchev, A., & Goerdt, S. (2007). Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. Biomarker Insights, 2, 128–146.PubMedGoogle Scholar
  18. 18.
    Boot, R. G., Renkema, G. H., Verhoek, M., Strijland, A., Bliek, J., de Meulemeester, T. M., et al. (1998). The human chitotriosidase gene. Nature of inherited enzyme deficiency. Journal of Biological Chemistry, 273, 25680–25685.PubMedCrossRefGoogle Scholar
  19. 19.
    Malaguarnera, L., Ohazuruike, L. N., Tsianaka, C., Antic, T., Di Rosa, M., & Malaguarnera, M. (2010). Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians. Journal of Human Genetics, 55, 8–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Lehrnbecher, T., Bernig, T., Hanisch, M., Koehl, U., Behl, M., Reinhardt, D., et al. (2005). Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia. Leukemia, 19, 1745–1750.PubMedCrossRefGoogle Scholar
  21. 21.
    Malaguarnera, L., Musumeci, M., Di Rosa, M., Scuto, A., & Musumeci, S. (2005). Interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages. Journal of Clinical Laboratory Analysis, 19, 128–132.PubMedCrossRefGoogle Scholar
  22. 22.
    Di Rosa, M., Zambito, A. M., Marsullo, A. R., Li Volti, G., & Malaguarnera, L. (2009). Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways. Journal of Cellular Biochemistry, 2009(107), 881–889.CrossRefGoogle Scholar
  23. 23.
    Fagone, P., Di Rosa, M., Palumbo, M., De Gregorio, C., Nicoletti, F., Malaguarnera, L. (2012, Jun 16). Modulation of heat shock proteins during macrophage differentiation. Inflammation Research.Google Scholar
  24. 24.
    Martinez, F. O., Gordon, S., Locati, M., & Mantovani, A. (2006). Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. Journal of Immunology, 177, 7303–7311.Google Scholar
  25. 25.
    Cakır, G., Gumus, S., Ucar, E., Kaya, H., Tozkoparan, E., Akgul, E. O., et al. (2012). Serum chitotriosidase activity in pulmonary tuberculosis: Response to treatment and correlations with clinical parameters. Annals of Laboratory Medicine, 32, 184–189.PubMedCrossRefGoogle Scholar
  26. 26.
    Bargagli, E., Margollicci, M., Nikiforakis, N., Luddi, A., Perrone, A., Grosso, S., et al. (2007). Chitotriosidase activity in the serum of patients with sarcoidosis and pulmonary tuberculosis. Respiration, 74, 548–552.PubMedCrossRefGoogle Scholar
  27. 27.
    Iyer, A., van Eijk, M., Silva, E., Hatta, M., Faber, W., Aerts, J. M., et al. (2009). Increased chitotriosidase activity in serum of leprosy patients: Association with bacillary leprosy. Clinical Immunology, 131, 501–509.PubMedCrossRefGoogle Scholar
  28. 28.
    Di Rosa, M., Mangano, K., De Gregorio, C., Nicoletti, F., & Malaguarnera, L. (2012). Association of chitotriosidase genotype with the development of nonalcoholic fatty liver disease. Hepatitis Research. doi:10.1111/j.1872-034X.2012.01063.x.
  29. 29.
    Martinez, F. O., Helming, L., & Gordon, S. (2009). Alternative activation of macrophages: an immunologic functional perspective. Annual Review of Immunology, 27, 451–483.PubMedCrossRefGoogle Scholar
  30. 30.
    Wynn, T. A., & Barron, L. (2010). Macrophages: master regulators of inflammation and fibrosis. Seminars in Liver Disease, 30, 245–257.PubMedCrossRefGoogle Scholar
  31. 31.
    Stein, M., Keshav, S., Harris, N., & Gordon, S. (1992). Interleukin 4 potently enhances murine macrophage mannose receptor activity: A marker of alternative immunologic macrophage activation. Journal of Experimental Medicine, 176, 287–292.PubMedCrossRefGoogle Scholar
  32. 32.
    Berry, A., Balard, P., Coste, A., Olagnier, D., Lagane, C., Authier, H., et al. (2007). IL-13 induces expression of CD36 in human monocytes through PPAR gamma activation. European Journal of Immunology, 37, 1642–1652.PubMedCrossRefGoogle Scholar
  33. 33.
    Kang, K., Reilly, S. M., Karabacak, V., Gangl, M. R., Fitzgerald, K., Hatano, B., et al. (2008). Adipocyte-derived Th2 cytokines and myeloid PPAR delta regulate macrophage polarization and insulin sensitivity. Cell Metabolism, 2008(7), 485–495.CrossRefGoogle Scholar
  34. 34.
    Pourcet, B., Feig, J. E., Vengrenyuk, Y., Hobbs, A., Kepka-Lenhart, D., Garabedian, M., et al. (2011). LXR{alpha} regulates macrophage arginase 1 through PU.1 and interferon regulatory factor 8. Circulation Research, 109, 492–501.PubMedCrossRefGoogle Scholar
  35. 35.
    Lee, C. G. (2009). Chitin, chitinases and chitinase-like proteins in allergic inflammation and tissue remodeling. Yonsei Medical Journal, 50, 22–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Michelino Di Rosa
    • 1
  • Giulia Malaguarnera
    • 1
  • Corinne De Gregorio
    • 1
  • Fabio D’Amico
    • 1
  • Maria Clorinda Mazzarino
    • 1
  • Lucia Malaguarnera
    • 1
  1. 1.Department of Bio-medical SciencesUniversity of CataniaCataniaItaly

Personalised recommendations