Up-regulation of C5a receptor expression and function on human monocyte derived dendritic cells by prostaglandin E2.

The expression of the C5a-receptor (C5aR) on dendritic cells, its regulation and function have not been well established thus far. We show that the C5aR is expressed on human monocyte-derived dendritic cells (DC) and can be down-regulated by maturation stimuli such as tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) or CD40L and by the T helper 1-cytokine interferon-gamma (INF-gamma). Prostaglandin E2 (PGE2), a proinflammatory mediator supporting dendritic cell activation and necessary for adequate DC migration, leads to the up-regulation of C5aR expression when incubated alone and prevents down-regulation when given in combination with TNF-alpha or LPS. Stimulation of C5aR on DC triggered F-actin polymerization, indicating the chemotactic potential of DC elicited by C5a. C5a induced F-actin polymerization was increased when C5aR was up-regulated by PGE2. Stimulation of DC with C5a resulted in interleukin-10 production which was significantly increased after C5aR up-regulation with TNF-alpha and PGE2. Therefore, up-regulation of the C5aR on human DC alters their chemotactic and immunologic response to C5a.