DIFFERENTIAL EXPRESSION OF MACROPHAGE INFLAMMATORY PROTEIN-2 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN EXPERIMENTAL GLOMERULONEPHRITIS

We examined the relation between glomerular expression of chemokines f rom alpha-subfamily (macrophage inflammatory protein-2, MIP-2) and bet a-subfamily (monocyte chemoattractant protein-1, MCP-1) and infiltrati on of neutrophils and monocytes in antibody mediated glomerulonephriti s in rats. In the accelerated model of nephrotoxic nephritis (NTN), gl omerular expression of MIP-2 and MCP-1 genes correlated with the seque ntial migration of neutrophil and monocyte influx, respectively. These relationships were investigated further in the heterologous phase of NTN by applying various treatments known to modulate the severity of i njury. Pretreatment with bacterial lipopolysaccharide resulted in grea ter injury, MIP-2 expression increased 25- to 50-fold, and the glomeru lar neutrophil count increased two- to fourfold. Both MIP-2 mRNA level s and neutrophil infiltration were reduced by additional pretreatment with IL-6, IL-1 receptor antagonist, soluble IL-1 receptor or soluble TNF receptor (Spearman correlation coefficient r = 0.897, P < 0.005). In the heterologous phase of NTN, different pre-treatments only result ed in trivial changes in MCP-1 expression and monocyte infiltration. I n conclusion, glomerular MIP-2 gene expression correlates with neutrop hil infiltration both temporally during the evolution of nephritis, an d when glomerular injury is modified by treatment. Glomerular MCP-1 ge ne expression correlates with monocyte influx. The data show chemokine s of alpha- and beta-subfamilies co-operative to cause selective and s equential migration of different leukocyte subsets during development of antibody mediated glomerulonephritis.