ANTI-VITRONECTIN ANTIBODIES ENHANCE ANTI-THY-1-INDUCED PROTEINURIA INPVG C, BUT NOT IN WISTAR RATS/

Injection of rats with mouse monoclonal IgG2a anti-Thy1.1 antibodies ( ER4G) results in rapid development of proteinuria in Wister rats, reac hing average values of 160 mg/24 h on day 3 after antibody administrat ion. In contrast, no overt proteinuria was observed in PVG/c+ rats (ma ximum, 40 mg/24 h on day 3). This study investigates whether differenc es in the inactivation of C5b-9 complexes in the glomerulus by complem ent inhibitors are responsible for the differences in proteinuria betw een the two rat strains. Regardless of the presence of proteinuria, an increased expression of Crry by mesangial cells (MC) was observed wit hin 24 h after injection of ER4G in both Wistar and PVG/c+ rats. Doubl e-label immunofluorescence using goat anti-mouse Ig antibodies demonst rated an expression of Crry exclusively on MC. Furthermore, Crry coloc alized with C5b-9 complexes on MC, as detected by a monoclonal antibod y against the rat C5b-9 neo-antigen. In PVG/c+ rats, C5b-9 complexes p ersisted in the mesangial area for at least 7 d and colocalized immedi ately (within 1 h) and homogeneously with vitronectin. However, in pro teinuric Wister rats, C5b-9 complexes disappeared from the glomerular mesangium within 6 d. In these rats, mesangial colocalization of C5b-9 with vitronectin could only occasionally be detected. Pretreatment of PVG/c+ rats with antibodies against vitronectin, followed by administ ration of ER4G, resulted in the immediate development of proteinuria ( maximum, 119 mg/24 h on day 3; P < 0.05), whereas Wistar rats did not become more proteinuric. This study provides evidence that differences in susceptibility of PVG/c+ and Wistar rats to complement-mediated da mage of the glomerulus may be related to the degree of inactivation of C5b-9 complexes by complement regulatory factors.