Functions of C5a receptors.
The split product of the complement protein, C5, is C5a and is an extremely potent pro-inflammatory peptide that interacts with two C5a receptors, C5aR and C5L2, present on surfaces of phagocytes as well as other cell types. The former is a well-established receptor that initiates G-protein-coupled signaling via mitogen-activated protein kinase pathways. Its in vivo blockade greatly reduces inflammatory injury. Much less is known about C5L2, occupancy of which by C5a does not initiate increased intracellular Ca(2+). There are numerous conflicting reports suggesting that C5L2 is a "default receptor" that attenuates C5a-dependent biological responses by competing with C5aR for binding of C5a. However, there are other reports suggesting that C5L2 plays an active, positive role in inflammatory responses. Better definition of C5L2 is needed if its in vivo blockade, along with C5aR, is to be considered in complement-dependent inflammatory diseases.
Ward
Peter A
PA
Department of Pathology, The University of Michigan Medical School, Ann Arbor, 48109-0602, USA. pward@umich.edu
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism*; D015937:Complement C5a, des-Arginine / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism* / Q000502:physiology; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
C417003:C5aR2 protein, human; D015937:Complement C5a, des-Arginine; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D015936:Complement C5a; D020928:Mitogen-Activated Protein Kinases