Cellular receptors to the anaphylatoxins C3a and C5a.
A single component in the plasma membrane of human polymorphonuclear leukocytes (hPMN) has been identified as the binding site for C5a. Labelled human C5a can be cross-linked to a 48,000-Mr membrane component on the hPMN surface by using the bifunctional reagent ethylene glycol bis(succinimidyl succinate). The membrane component is believed to be the C5a receptor or the binding subunit of a C5a receptor complex. Our ligand-uptake data indicate that the hPMN has high-affinity binding sites for C5a with a Kd of the order of 1-2 nM and an estimated 50,000-113,000 binding sites/cell. Preliminary binding studies of C3a and C5a to rat peritoneal mast cells indicate that non-specific uptake by these cells is so great that it obscures characterization of specific receptor interactions. Data recently reported [Gervasoni, Conrad, Hugli, Schwartz & Ruddy (1986) J. Immunol. 136, 285-292] suggest that non-specific binding of C3a to mast cells is caused by electrostatic interactions between the cationic ligand and anionic heparin-proteoglycan on the cell surface, with an additional complication of the bound ligand undergoing proteolytic degradation. It is therefore proposed that synthetic analogue peptides designed to minimize non-specific interactions with the cell will be useful tools for demonstrating anaphylatoxin receptors on mast cells and may prove essential for receptor isolation.
D000818:Animals; D003182:Complement C5 / Q000378:metabolism; D015936:Complement C5a; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D016177:Macrophage-1 Antigen; D008407:Mast Cells / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010455:Peptides; D051381:Rats; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000302:isolation & purification*
D003182:Complement C5; D016177:Macrophage-1 Antigen; D010455:Peptides; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a