Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity.
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.
van Eijk
Marco
M
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
van Roomen
Cindy P A A
CP
Renkema
G Herma
GH
Bussink
Anton P
AP
Andrews
Laura
L
Blommaart
Edward F C
EF
Sugar
Alan
A
Verhoeven
Arthur J
AJ
Boot
Rolf G
RG
Aerts
Johannes M F G
JM
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*
D002686:Chitin; D016179:Granulocyte Colony-Stimulating Factor; D006596:Hexosaminidases; C086400:chitotriosidase