Insight into the evolution of anaphylatoxin receptors through the study of c3a and c5a receptors in rainbow trout (oncorhynchus mykiss)

Résumé

Activation of the complement system results in the generation of anaphylatoxins C3a, C4a and C5a. In mammals, it has been shown that C3a and C5a elicit biological responses through their interactions with C3 and C5 receptors respectively. Although both receptors share a high degree of homology, until recently, very little was understood about the evolution of these receptors. In particular, it was not known whether or not these receptors were represented by a single common ancestral molecule in lower vertebrates. Here, we present the clonning and functional characterization of bona fise C3aR and C5aR in rainbow trout. While both receptors share a high degree of homology with their mammalian counterparts, the secondary structure of C3aR is unique in its truncated second extracellular loop. Antibodies generated against C3aR inhibited trout C3a-mediated intracellular calcium mobilization in trout leukocytes. While recombinantly expressed C5a was able to induce chemotaxis in trout peripheral leukocytes, antibodies generated against C5aR were found to inhibit this activity. Both C3aR and C5aR are expressed primary on B-cells, and to a lesser extent, on granulocytes. Our resluts indicate that, although highly homologous, the divergence of these two molecules into distinct receptors occurred prior to the emergence of teleost fish.