Abstract

Fibrinogen (fgn) readily coats surfaces, and has been implicated in inflammation, but its role is still ill-defined. Available evidence suggests it is adsorbed fgn that operates during inflammation. To better elucidate the role of adsorbed fgn, the protein was first bound to the surface of microscopic polymeric beads and then placed in the presence of human dendritic cells (hDC’s). Immature DC (iDC’s) produce more IL-6, IL-8 and MIP-1β and mature DC’s (mDC’s) produce more IL-6, MCP-1 and MIP-1β in response to adsorbed fgn than they do in response to solution phase fgn. IL-6 and MIP-1β production by iDC’s are reduced by anti-TLR4, anti-CD18 and anti-CD11c antibodies. IL-8 production by iDC’s is reduced by antibodies against CD11b, CD18 and TLR4. Only anti-TLR4 antibodies reduce IL-6 and MIP-1β production by mDC’s, while MCP-1 production is reduced by antibodies against CD18, CD11c and TLR4. The increased production of these inflammatory mediators by hDC’s in response to adsorbed fgn might enhance immune cell recruitment, thereby potentiating inflammation. These data also suggest that certain fgn receptors play a role in fgn-elicited production of IL-6, IL-8, MCP-1 and MIP-1β by hDC’s.

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