Response-selective C5a agonists: differential effects on neutropenia and hypotension in the rat

Some in vivo activities of two complement C5a agonist analogues have been e valuated by measuring changes in blood pressure and neutropenia in the rat and comparing the results with their receptor affinities in peritoneal macr ophages and polymorphonuclear leucocytes (PMNs). In vitro C5a receptor (C5a R) binding experiments showed that YSFKPMPLaR and YSFKD(NMeNle)PlaR had sim ilar affinities for the macrophage C5aR (IC50 0.2, 0.1 mM respectively). In PMNs, the affinity of YSFKPMPLaR (IC50 0.1 mM) was similar to that in macr ophages, whereas the affinity of YSFKD(NMeNle)PLaR for the PMN C5aR was > 1 00mM. Given i.v., YSFKD(NMeNle)PLaR had similar activity to YSFKPMPLaR on b lood pressure but did not cause neutropenia.. These results demonstrate sel ectivity of a new C5a agonist in vitro, which is paralleled in vivo. The re sults suggest the possibility of developing selective agonists of C5a for i n vivo use in humans.