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.
Weinmann
Oliver
O
Department of Dermatology and Allergology, Hannover Medical University, Hannover, Germany.
Gutzmer
Ralf
R
Zwirner
Jörg
J
Wittmann
Miriam
M
Langer
Katja
K
Lisewski
Margarete
M
Mommert
Susanne
S
Kapp
Alexander
A
Werfel
Thomas
T
D000199:Actins / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods; D011108:Polymers / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000199:Actins; D019013:CD40 Antigens; D008070:Lipopolysaccharides; D011108:Polymers; D044087:Receptor, Anaphylatoxin C5a; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D015232:Dinoprostone