CB: Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody

The role of the chemokine, macrophage inflammatory pro-tein-2 (MIP-2), during anti-glomerular basement mem-brane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Re-combinant rat MIP-2 (rMIP-2) from Escherichia coli exhib-ited neutrophil chemotactic activity and produced neutro-phil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40 % at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54 % at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evi-denced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat. (J. Clin. Invest. 1995. 95:1009-1017.) Key words: macrophage inflamma-tory protein-2 * anti-glomerular basement membrane glo-merulonephritis * anti-macrophage inflammatory protein-2 antibody * neutrophils * chemokin