The chemotactic receptor for human C5a anaphylatoxin

Abstract

Host defence and inflammatory responses are controlled and amplified by receptor-mediated events often initiated by a chemotactic factor that directs the approach of phagocytic cells. Complement receptors CR1 and CR3 are responsible for the phagocytic and adhesive properties of neutrophils, whereas the C5a receptor mediates the pro-inflammatory and chemotactic actions of the complement anaphylatoxin C5a. In addition to stimulating chemotaxis, granule enzyme release and superoxide anion production, this receptor stimulates upregulation of expression and activity of the adhesion molecule MAC-1, and of CR1, and a decrease in cell-surface glycoprotein 100MEL-14 on neutrophils. In vivo, the C5a receptor may participate in anaphylactoid and septic shock. The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells. The deduced amino-acid sequence of the receptor reveals the expected motifs befitting its interaction with cellular GTP-binding proteins.