Interleukin-8 alters glomerular heparan sulfate glycosaminoglycan chain size and charge in rats

We have previously shown that the in vivo infusion of interleukin-8 (IL8) in rats causes albuminuria and an increased catabolism of the heparan sulfate (HS) glycosaminoglycans (GAG). The purpose of this study was to characterize further the in vivo effect of IL8 on rat HSGAG. The left renal artery of male rats was continuously infused with IL8 (750 ng/ml, 4 rats) or 1% bovine serum albumin (3 rats) using an osmotic pump. On the 5th day of infusion, 35sulfate (1.0 mCi/100 g) was given intraperitoneally and the rat was killed 8 h later. Glomerular HSGAG was isolated and its size and charge was determined by liquid chromatography. The HSGAG 35sulfate uptake was higher in IL8-treated rats than controls (387+/-138 vs. 246+/-15 cpm/1,000 glomeruli, mean +/- SD, P<0.05). No differences in HSGAG size were observed between IL8-treated and control animals. However, after ion exchange chromatography, there was a shift to the left in the elution profile of IL8-treated rats, demonstrating the presence of chains with decreased negative charge. IL8 infusion into rats results in a decreased total negative charge of the HSGAG. Because IL8 has been found in the serum of some patients with minimal lesion nephrotic syndrome, this finding may explain, at least in part, the reported reduced glomerular charge barrier observed in these patients.