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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Regulation of cytosolic phospholipase A
2
activation and cyclooxygenase 2 expression in macrophages by the β-glucan receptor
Journal of Biological Chemistry, Volume 281, No. 9, Year 2006
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Description
Phagocytosis of non-opsonized microorganisms bymacrophages initiates innate immune responses for host defense against infection. Cytosolic phospholipase A2 is activated during phagocytosis, releasing arachidonic acid for production of eicosanoids, which initiate acute inflammation. Our objective was to identify pattern recognition receptors that stimulate arachidonic acid release and cyclooxygenase 2 (COX2) expression in macrophages by pathogenic yeast and yeast cell walls. Zymosan- and Candida albicans-stimulated arachidonic acid release from resident mouse peritoneal macrophages was blocked by soluble glucan phosphate. In RAW264.7 cells arachidonic acid release, COX2 expression, and prostaglandin production were enhanced by overexpressing the β-glucan receptor, dectin-1, but not dectin-1 lacking the cytoplasmic tail. Pure particulate (1, 3)-β-D-glucan stimulated arachidonic acid release and COX2 expression, which were augmented in a Toll-like receptor 2 (TLR2)-dependent manner by macrophage-activating lipopeptide-2. However, arachidonic acid release and leukotriene C4 production stimulated by zymosan and C. albicans were TLR2-independent, whereas COX2 expression and prostaglandin production were partially blunted in TLR2-/- macrophages. Inhibition of Syk tyrosine kinase blocked arachidonic acid release and COX2 expression in response to zymosan, C. albicans, and particulate (1, 3)-β-D-glucan. The results suggest that cytosolic phospholipase A2 activation triggered by the β-glucan component of yeast is dependent on the immunoreceptor tyrosine-based activation motif-like domain of dectin-1 and activation of Syk kinase, whereas both TLR2 and Syk kinase regulate COX2 expression. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Authors & Co-Authors
Suram, Saritha
United States, Denver
National Jewish Medical and Research Center
Brown, Gordon D.A.
South Africa, Cape Town
University of Cape Town
Ghosh, Moumita
United States, Denver
National Jewish Medical and Research Center
Gordon, Siamon
United Kingdom, Oxford
Sir William Dunn School of Pathology
United States, Aurora
University of Colorado Anschutz Medical Campus
Loper, Robyn
United States, Denver
National Jewish Medical and Research Center
Taylor, Philip Russel
United Kingdom, Oxford
Sir William Dunn School of Pathology
United States, Aurora
University of Colorado Anschutz Medical Campus
Akira, Shizuo
Japan, Suita
Research Institute for Microbial Diseases
Uematsu, Satoshi
Japan, Suita
Research Institute for Microbial Diseases
Williams, David L.
United States, Johnson
Quillen-dishner College of Medicine
Leslie, Christina C.
United States, Denver
National Jewish Medical and Research Center
United Kingdom, Oxford
Sir William Dunn School of Pathology
United States, Aurora
University of Colorado Anschutz Medical Campus
Statistics
Citations: 136
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1074/jbc.M509824200
ISSN:
00219258
e-ISSN:
1083351X