MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN CHRONIC PROLIFERATIVE IMMUNE-COMPLEX NEPHRITIS

In rats with chronic serum sickness, proliferative immune complex glom erulonephritis progresses in three discrete stages, designated mild, m oderate, and severe. One distinguishing immunopathologic feature, the progressive increase in the number of glomerular macrophages, is close ly correlated with decreasing kidney function. We hypothesized that mo nocyte chemoattractant protein-1, a beta-subfamily chemokine with pote nt monocyte-specific chemotactic activity, might contribute to this ma crophage accumulation. Immunohistochemical methods were used to identi fy monocyte chemoattractant protein-1 in kidney tissue sections. Total RNA was extracted from the kidneys of rats at each stage of chronic s erum sickness, and age-matched controls, and Northern blot analysis wa s performed with a rat monocyte chemoattractant protein-1 cDNA probe. Tissue staining localized monocyte chemoattractant protein-1 to the gl omerular capillary wall and mesangium in chronic serum sickness. Minim al quantities of monocyte chemoattractant protein-1 mRNA were detected in the kidneys of normal control rats, with marked increases in mRNA as chronic serum sickness nephritis progressed to the moderate stage. There was then an apparent decrease in monocyte chemoattractant protei n-1 mRNA in the severe stage. The degree of protein staining and mRNA levels paralleled each other. We conclude that monocyte chemoattractan t protein-1 is a potentially important chemotactic agent in chronic se rum sickness nephritis. (C) 1996 Academic Press, Inc.