Taxonomic group: fungi / Ascomycota
(Phylum: Ascomycota)
Organ / tissue: mycelium
NCBI PubMed ID: 19575004Publication DOI: 10.1038/aps.2009.93Journal NLM ID: 100956087Publisher: New York: Nature Publishing Group
Correspondence: Gao XD <xiangdong_gao
yahoo.com.cn>
Institutions: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
YCP, a novel (1,4)-α-D-glucan, was isolated from the mycelium of the marine filamentous fungus Phoma herbarum YS4108. In this work, we investigated a YCP-binding cellular receptor expressed by macrophages and the intracellular signal transduction pathways involved in YCP-induced macrophage activation. Fluorescence-labeled YCP (fl-YCP) was prepared using the CDAP-activation method. Fluorescence confocal laser microscopy and fluorescence-activated cell sorting (FACS) were used to analyze the effect of fl-YCP on macrophages. To characterize the properties of the YCP receptor, carbohydrates and antibodies were used to inhibit the binding of fl-YCP to macrophages. Moreover, we investigated the role of membrane receptors Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), Toll-like receptor 6 (TLR6) and complement receptor 3 (CR3). We also examined the role of the p38 kinase pathway in mediating nitric oxide (NO) production. YCP had an in vitro stimulatory effect on the release of NO in macrophage, and fl-YCP can bind directly to receptors on the surface of macrophages in a time- and dose-dependent manner. Competition studies show that LPS, laminarin, anti-TLR4 antibody and anti-CD11b (CR3) antibody could inhibit fl-YCP binding to macrophages. Conversely, mannose, anti-TLR2 and anti-TLR6 antibody could not. Treatment of RAW264.7 cells with YCP resulted in significant activation of p38 in a time-dependent manner. The specific p38 inhibitor SB203580 abrogated YCP-induced NO generation. Treatment of RAW264.7 cells with anti-TLR4 antibody and anti-CR3 antibody significantly reduced YCP-induced NO production and p38 activation. We have demonstrated that YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a p38 kinase-dependent manner in macrophages
macrophages, receptor, nitric oxide, Phoma herbarum, YCP, p38 kinase
Structure type: homopolymer ; 2400000
Location inside paper: p. 1008, right column, paragraph 1, reference 1
Trivial name: α-(1,4)-glucan
Compound class: glucan, polysaccharide
Contained glycoepitopes: IEDB_140629,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_420417,IEDB_420418,IEDB_420421,IEDB_857742,IEDB_983931,SB_192
Methods: inhibition studies, Western blotting, GPC, immunoblotting, ion-exchange chromatography, extraction, CC, cell growth, flow cytometry analysis, confocal microscopy, determination of NO production, fluorescence labeling, precipitation
Biological activity: polysaccharide is capable of inducing NO production from macrophages through TLR4 and CR3 pathways
Related record ID(s): 49221, 49223, 50866
NCBI Taxonomy refs (TaxIDs): 73001Reference(s) to other database(s): GTC:G05740LL
Show glycosyltransferases
There is only one chemically distinct structure:
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