EXPRESSION AND FUNCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN EXPERIMENTAL NEPHROTIC SYNDROME

This study investigates the expression and function of monocyte chemoa ttractant protein-1 (MCP-1) in rats with aminonucleoside nephrosis ind uced by a single intraperitoneal injection of puromycin aminonucleosid e (PAN), On Day 7, PAN-treated rats had a sixfold increase in renal MC P-1 messenger (m)RNA levels and a twofold increase in interleukin-1 be ta mRNA levels, During the course of PAN nephrosis, most of the de nov o MCP-1 protein resembled protein droplets that were prominent in glom eruli between Days 3 and 14 and weaker but visible in tubules between Days 5 and 10. In addition, occasional tubules showed a cytoplasmic st aining pattern for MCP-1. Two studies evaluated the effect of MCP-1 ne utralization on renal monocyte recruitment, In the first study, PAN-tr eated rats were treated with affinity-purified MCP-1-neutralizing rabb it 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; 1 06 +/- 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 w ith nephrotic rats treated with nonimmune rabbit IgG. In the second st udy, a group of PAN-treated rats was treated with MCP-l-neutralizing I gG administered continuously by an intraperitoneal miniosmotic pump fo r 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 int raglomerular 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 sugg est that although MCP-1 gene and protein expression are increased in t he kidneys of rats with aminonucleoside nephrosis, MCP-1 does not appe ar to play an essential role in early renal monocyte recruitment in th is model. (C) 1996 Academic Press, Inc.