GLOMERULAR INJURY-INDUCED BY CATIONIC 70-KD STAPHYLOCOCCAL PROTEIN - SPECIFIC IMMUNE-RESPONSE IS NOT INVOLVED IN EARLY PHASE IN RATS

A highly cationic staphylococcal protein (designated p70, MW 70 kD, pI <10) belongs to the groups of bacterial proteins that can bind immunog lobulin without specific antigen-antibody recognition; heparin inhibit ion tests indicated a charge interaction. This study evaluated the nep hritogenicity of p70, which has affinity for the glomerular basement m embrane (GBM), and the influence of various mediator systems on the in duction of glomerulonephritis by p70. The left kidneys of intact rats, rats given cobra venom factor (complement-depleted), or rats given an ti-adhesion molecules (ICAM-1 and LFA-1a) mere perfused with p70. Prot einuria started within 24 h and persisted at day 5. Intraglomerular in filtration of cells was seen as early as 15 min, peaking at day 1. Dep osits of rat IgC and C3 mere seen in a subendothelial location 15 min after p70 perfusion in the left kidney and mere found in a predominant ly subepithelial location from 1 day onwards. Complement depletion and blockade of adhesion molecules suppressed proteinuria from day 2 onwa rds; these manipulations also prevented the recruitment of infiltratin g cells and partially hindered the transfer of IgG across the GBM and the accumulation of IgG in the subepithelial region. In the non-perfus ed right kidneys, deposits of Ige and C3 were comparable to those in t he left kidneys, suggesting that p70-IgG complexes formed in the circu lation may also contribute to the deposits in the GEM. Heparin inhibit ion tests indicated an electrostatic interaction between p70 and immun oglobulin. Complement and inflammatory mediator systems (granulocytes, monocytes/macrophages, and/or lymphocytes) mere required to provoke g lomerular injury. p70 might play a role in acute glomerulonephritis fo llowing Staphylococcus aureus infection. (C) 1998 John Wiley & Sons, L td.