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International Immunology Advance Access published online on October 7, 2005
International Immunology, doi:10.1093/intimm/dxh328
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received May 30, 2005
Accepted August 26, 2005

Article

Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity

Marco van Eijk 1, Cindy P. A. A. van Roomen 1, G. Herma Renkema 2, Anton P. Bussink 1, Laura Andrews 3, Edward F. C. Blommaart 1, Alan Sugar 4, Arthur J. Verhoeven 5, Rolf G. Boot 1, and Johannes M. F. G. Aerts 1*

1 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands
2 Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands; Present address: Department of Virology, Institute of Medical Technology and Tampere University Hospital, Tampere FN-33014, Finland
3 Genzyme Corporation, Framingham, MA 01701, Du Pont, USA
4 Section of Infectious Diseases, Evan Memorial Department of clinical Research, Boston Medical Center, Boston, MA 02118, USA
5 Sanquin Research at CLB, Amsterdam, The Netherlands

* To whom correspondence should be addressed.
Johannes M. F. G. Aerts, E-mail: j.m.aerts{at}amc.uva.nl


  Abstract

Man has been found to produce highly conserved chitinases. The most prominent is the phagocyte-derived chitotriosidase, the plasma levels of which are markedly elevated in some pathological conditions. Here, we report that both polymorphonuclear neutrophils (PMNs) and macrophages (m{phi}) are a source of chitotriosidase. The enzyme is located in specific granules of human PMNs and secreted following stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, GM-CSF induces expression of chitotriosidase in m{phi} that constitutively secrete the enzyme and partly accumulate it in their lysosomes. Studies with recombinant human chitotriosidase revealed that the enzyme targets chitin-containing fungi. These findings are consistent with earlier observations concerning anti-fungal activity of homologous plant chitinases and beneficial effects of GM-CSF administration in individuals suffering from invasive fungal infections. In conclusion, chitotriosidase should be viewed as a component of the innate immunity that may play a role in defence against chitin-containing pathogens and the expression and release of which by human phagocytes is highly regulated.

Keywords: human; monocyte/macrophage; neutrophil.
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