Differential activation of murine macrophages by angelan and LPS.
In our previous studies, we showed that angelan, a polysaccharide purified from Angelica gigas Nakai, is a potent LPS-mimetic in murine macrophages [Jeon, Y.J., Han, S.B., Ahn, K.S., Kim, H.M., 1999. Activation of NF-kB/Rel in angelan-stimulated macrophages. Immunopharmacology 43, 1-9]. Angelan stimulates murine macrophage to produce cytokines including iNOS and activate NF-kappaB/Rel. In the present study, we investigated the role of CD14 and complement receptor type 3 (CR3) in mediating NO production and NF-kappaB/Rel activation induced by angelan and LPS. Three major differences between angelan and LPS were observed. First, angelan does not require serum proteins for NO response and NF-kappaB/Rel activation, while the activation by LPS requires serum proteins. Second, blocking of either CD14 or CR3 decreased angelan-induced NO response, while LPS-mediated NO production was inhibited by anti-CD14 mAb only. Third, angelan induced strong NF-kappaB/Rel and slight AP-1 DNA binding, whereas LPS potently activated both NF-kappaB/Rel and AP-1. Both angelan and LPS degraded IkappaB proteins and subsequently induced the mobilization of NF-kappaB/Rel proteins (p65, c-rel and p50) into nucleus. This suggests that macrophages display a common signaling machinery leading to the NF-kappaB/Rel activation in response to different stimulants. In conclusion, angelan and LPS use the membrane receptor CD14 and CR3 differentially for signaling NF-kappaB/Rel activation and NO production.
Jeon
Y J
YJ
Korea Research Institute of Bioscience and Biotechnology (KRIBB), PO Box 115, Yusong, 305-600, Taejon, South Korea.
Han
S B
SB
Ahn
K S
KS
Kim
H M
HM
D000209:Acute-Phase Proteins; D000818:Animals; D019661:Apiaceae; D001202:Ascitic Fluid / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D017252:CD3 Complex; D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D007106:Immune Sera; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009569:Nitric Oxide; D009573:Nitrites; D009687:Nuclear Proteins; D011134:Polysaccharides; D000099231:Lipopolysaccharide-Binding Protein