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Macrophage receptors of polysaccharide isolated from a marine filamentous fungus Phoma herbarum YS4108.
- Source :
- Acta Pharmacologica Sinica; Jul2009, Vol. 30 Issue 7, p1008-1014, 7p, 1 Diagram, 5 Graphs
- Publication Year :
- 2009
-
Abstract
- AbstractAim: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.Methods: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.Results: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.Conclusion:We have demonstrated that YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a p38 kinase-dependent manner in macrophages.Acta Pharmacologica Sinica (2009) 30: 1008–1014; doi: 10.1038/aps.2009.93 [ABSTRACT FROM AUTHOR]
- Subjects :
- MACROPHAGES
POLYSACCHARIDES
FILAMENTOUS fungi
PHOMA
NITRIC oxide
Subjects
Details
- Language :
- English
- ISSN :
- 16714083
- Volume :
- 30
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Acta Pharmacologica Sinica
- Publication Type :
- Academic Journal
- Accession number :
- 42972102
- Full Text :
- https://doi.org/10.1038/aps.2009.93