title: Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity.
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) 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 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.
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van Eijk
authors.forename: Cindy P A A
authors.initials: CP
authors.lastname: van Roomen
authors.forename: G Herma
authors.initials: GH
authors.lastname: Renkema
authors.forename: Anton P
authors.initials: AP
authors.lastname: Bussink
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Edward F C
authors.initials: EF
authors.lastname: Blommaart
authors.forename: Alan
authors.initials: A
authors.lastname: Sugar
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Verhoeven
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Boot
authors.forename: Johannes M F G
authors.initials: JM
authors.lastname: Aerts
mesh_terms: D002478:Cells, Cultured; D002686:Chitin / Q000276:immunology / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006596:Hexosaminidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009181:Mycoses / Q000188:drug therapy / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism*
chemical_list: D002686:Chitin; D016179:Granulocyte Colony-Stimulating Factor; D006596:Hexosaminidases; C086400:chitotriosidase