Plasma clearance of the human C5a anaphylatoxin by binding to leucocyte C5a receptors.
The C5a anaphylatoxin is a potent complement-derived mediator of inflammation with chemotactic activity. In this study the possible role of specific high-affinity binding sites for C5a on peripheral blood leucocytes for the removal of C5a from human blood plasma was investigated. The addition of purified granulocytes or mononuclear cells to complement-activated plasma resulted in the rapid and dose-dependent removal of up to 80% of plasma C5a, as determined by ELISA. The specific role of leucocyte C5a receptors (C5aR) in the plasma clearance of C5a was demonstrated by the inhibition of C5a uptake by the preincubation of cells with the C5aR-specific monoclonal antibody S5/1. Furthermore, U937 cells which had been induced by db-cAMP to express C5aR, but not undifferentiated U937 cells, were capable of removing C5a from plasma. The inhibition of C5aR internalization by monensin did not affect C5a uptake by leucocytes. The co-incubation with leucocytes had no effect on the plasma clearance of complement activation products C3a or terminal complement complex (TCC), as determined by this in vitro assay. The binding of the C5a anaphylatoxin to cellular receptors represents an effective control mechanism that protects the organism from systemic effects of this potent phlogistic mediator.
Department of Immunology, University of Göttingen, Germany.
M
M
Oppermann
O
O
Götze
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D015926:Complement C3a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism*; D015937:Complement C5a, des-Arginine / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015937:Complement C5a, des-Arginine; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C047610:SC5b-9 protein complex; D015926:Complement C3a; D015936:Complement C5a; D003165:Complement System Proteins