C3A AND C5A ANAPHYLATOXINS RECEPTORS

The complement is one of the oldest defence systems of the body. Altho ugh this system is primarily known for its killing function of pathoge ns, it can also be involved in immune and inflammatory reactions such as phagocytosis of foreign particles or recruitment of immune cells th rough chimiotactic peptides. Recent datas emerging from studies on loc al biosynthesis of complement suggest the involvement of some compleme nt components in non immune functions in tissues. The C3a and C5a anap hylatopxins, two inflammatory peptides released during complement acti vation, might have putative roles in tissues, in addition of their pro inflammatory properties. This hypothesis arises from the observation t hat the expression of their respective receptors, C3aR and C5aR, initi ally thought to be restricted to immune cells, appears to be enlarged to several tissues of the body. The C5aR is present on the surface of non myeloid cells of the liver and lung and on brain cells. C5a anaphy latoxin could thus be implicated in physiological processes and interf ere during pathological conditions in these tissues. The C5aR seems to play a predominant role in mucosal defence in lung. On the contrary, binding of C5a to its receptor seems to have a deletorious effect in k idney and joints during glomerulonephritis and inflammatory arthritis. Thus, a complete knowledge of the C5aR biology appears to be predomin ant in the inflammatory processes understanding. Dealing with the C3aR , data are more limited. However, the recent cDNA cloning of the human C3aR has already allowed the demonstration of a very large tissue exp ression of this receptor. Taken together, these observations argue for new physiological roles of C3a and C5a anaphylatoxins in tissues, in addition of their more classical inflammatory functions during patholo gical conditions.