Expression and function of monocyte chemoattractant protein-1 in experimental nephrotic syndrome

This study investigates the expression and function of monocyte chemoattractant protein-1 (MCP-1) in rats with aminonucleoside nephrosis induced by a single intraperitoneal injection of puromycin aminonucleoside (PAN). On Day 7, PAN-treated rats had a sixfold increase in renal MCP-1 messenger (m)RNA levels and a twofold increase in interleukin-1 beta mRNA levels. During the course of PAN nephrosis, most of the de novo MCP-1 protein resembled protein droplets that were prominent in glomeruli between Days 3 and 14 and weaker but visible in tubules between Days 5 and 10. In addition, occasional tubules showed a cytoplasmic staining pattern for MCP-1. Two studies evaluated the effect of MCP-1 neutralization on renal monocyte recruitment. In the first study, PAN-treated rats were treated with affinity-purified MCP-1-neutralizing rabbit IgG on Days 0, 1, 3, and 5; kidneys were harvested on Day 7. There was no difference in the mean number of interstitial macrophages [119 +/- 28 vs 88 +/- 9 ED-1+ cells/1000 tubulointerstitial (TI) cells; 106 +/- 28 vs 119 +/- 33 Ia+ cells/1000 TI cells] or intraglomerular macrophages [2.0 +/- 0.9 vs 1.7 +/- 0.5 ED-1+ cells/glomerular cross section (gcs); 1.2 +/- 0.3 vs 1.1 +/- 0.4 Ia+ cells/gcs] compared with nephrotic rats treated with nonimmune rabbit IgG. In the second study, a group of PAN-treated rats was treated with MCP-1-neutralizing IgG administered continuously by an intraperitoneal miniosmotic pump for 7 days and was compared with a control group treated in an identical fashion with PAN and nonimmune IgG. On Day 7 there was no difference in the mean number of interstitial macrophages (55 +/- 45 vs 67 +/- 16 ED-1+ and 70 +/- 63 vs 61 +/- 13 Ia+ cells/1000 TI cells) and intraglomerular macrophages (1.0 +/- 0.4 vs 1.6 +/- 0.9 ED-1+ and 0.6 +/- 0.1 vs 1.1 +/- 0.7 Ia+ cells/gcs). The results of this study suggest that although MCP-1 gene and protein expression are increased in the kidneys of rats with aminonucleoside nephrosis, MCP-1 does not appear to play an essential role in early renal monocyte recruitment in this model.