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

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

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267 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)1505-1512
JournalInternational Immunology
Volume17
Issue number11
DOIs
Publication statusPublished - 2005

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