Monocyte chemoattractant protein-1 in chronic proliferative immune complex nephritis

In rats with chronic serum sickness, proliferative immune complex glomerulonephritis progresses in three discrete stages, designated mild, moderate, and severe. One distinguishing immunopathologic feature, the progressive increase in the number of glomerular macrophages, is closely correlated with decreasing kidney function. We hypothesized that monocyte chemoattractant protein-1, a beta-subfamily chemokine with potent monocyte-specific chemotactic activity, might contribute to this macrophage accumulation. Immunohistochemical methods were used to identify monocyte chemoattractant protein-1 in kidney tissue sections. Total RNA was extracted from the kidneys of rats at each stage of chronic serum sickness, and age-matched controls, and Northern blot analysis was performed with a rat monocyte chemoattractant protein-1 cDNA probe. Tissue staining localized monocyte chemoattractant protein-1 to the glomerular capillary wall and mesangium in chronic serum sickness. Minimal 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 protein-1 mRNA in the severe stage. The degree of protein staining and mRNA levels paralleled each other. We conclude that monocyte chemoattractant protein-1 is a potentially important chemotactic agent in chronic serum sickness nephritis.