Differential activation of murine macrophages by angelan and LPS

Abstract

In our previous studies, we showed that angelan, a polysaccharide purified from Angelicagigas 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-κB/Rel. In the present study, we investigated the role of CD14 and complement receptor type 3 (CR3) in mediating NO production and NF-κB/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-κB/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-κB/Rel and slight AP-1 DNA binding, whereas LPS potently activated both NF-κB/Rel and AP-1. Both angelan and LPS degraded IκB proteins and subsequently induced the mobilization of NF-κB/Rel proteins (p65, c-rel and p50) into nucleus. This suggests that macrophages display a common signaling machinery leading to the NF-κB/Rel activation in response to different stimulants. In conclusion, angelan and LPS use the membrane receptor CD14 and CR3 differentially for signaling NF-κB/Rel activation and NO production.