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 [J eon, Y.J., Han, S.B., Ahn, K.S,, Kim, H.M., 1999. Activation of NF-kappa B/ Rel in angelan-stimulated macrophages. Immunopharmacology 43, 1-9]. Angelan stimulates murine macrophage to produce cytokines including iNOS and activ ate NF-kappa B/Rel. In the present study, we investigated the role of CD14 and complement receptor type 3 (CR3) in mediating NO production and NK-kapp a B/Rel activation induced by angelan and LPS. Three major differences betw een angelan and LPS were observed. First, angelan does not require serum pr oteins for NO response and NF-kappa B/Rel activation, while the activation by LPS requires serum proteins. Second, blocking of either CD14 or CR3 decr eased angelan-induced NO response, while LPS-mediated NO production was inh ibited by anti-CD14 mAb only. Third, angelan induced strong NF-kappa B/Rel and slight AP-1 DNA binding, whereas LPS potently activated both NF-kappa B /Rel and AP-1. Both angelan and LPS degraded I kappa B proteins and subsequ ently induced the mobilization of NF-kappa B/Rel proteins (p65, c-rel acid p50) into nucleus. This suggests that macrophages display a common signalin g machinery leading to the NF-kappa B/Rel activation in response to differe nt stimulants. In conclusion, angelan and LPS use the membrane receptor CD1 4 and CR3 differentially for signaling NF-kappa B/Rel activation and NO pro duction. (C) 2000 Elsevier Science B.V. All rights reserved.