Les récepteurs des anaphylatoxines C3a (C3aR) et C5a (C5aR).

Abstract

L’ancienneté du système du complément, dont le rôle principal est la défense antibactérienne de l’organisme, a fait envisager l’implication de certains de ses composants dans des fonctions non immunes au sein des tissus. Les anaphylatoxines C3a et C5a, peptides libérés lors de l’activation du complément, sont des médiateurs prépondérants de l’inflammation. La distribution très large de leurs récepteurs respectifs, C3aR et C5aR, indique que ces deux peptides pourraient exercer d’autres activités au sein des tissus. Le C5aR, présent à la surface de cellules non myéloïdes dans le foie, le poumon et le cerveau, semble jouer un rôle majeur dans la défense antimicrobienne au sein du poumon. Inversement, l’interaction de C5a avec son récepteur aurait un effet délétère dans le rein et les articulations lors de glomérulonéphrites ou d’arthrites inflammatoires. Le clonage récent de l’ADNc du C3aR a déjà permis d’entrevoir une large distribution cellulaire et tissulaire de ce récepteur, non limitée aux cellules immunes.

The complement is one of the oldest defence systems of the body. Although this system is primarily known for its killing function of pathogens, it can also be involved in immune and inflammatory reactions such as phagocytosis of foreign particles or recruitment of immune cells through chimiotactic peptides. Recent datas emerging from studies on local biosynthesis of complement suggest the involvement of some complement components in non immune functions in tissues. The C3a and C5a anaphylatoxins, two inflammatory peptides released during complement activation, might have putative roles in tissues, in addition of their proinflammatory properties. This hypothesis arises from the observation that the expression of their respective receptors, C3aR and C5aR, initially 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 anaphylatoxin could thus be implicated in physiological processes and interfere 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 deleterious effect in kidney and joints during glomerulonephritis and inflammatory arthritis. Thus, a complete knowledge of the C5aR biology appears to be predominant 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 expression 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 pathological conditions. [References: 41]