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) i n rats causes albuminuria and an increased catabolism of the heparan sulfat e (HS) glycosaminoglycans (GAG). The purpose of this study was to character ize further the in vivo effect of IL8 on rat HSGAG. The left renal artery o f male rats was continuously infused with IL8 (750 ng/ml, 4 rats) or 1% bov ine serum albumin (3 rats) using an osmotic pump. On the 5th day of infusio n, (35)sulfate (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;(35)sulfate uptake was high er in IL8-treated rats than controls (387+/-138 vs. 246+/-15 cpm/1,000 glom eruli, mean +/- SD, P<0.05). No differences in HSGAG size were observed bet ween IL8-treated and control animals. However after ion exchange chromatogr aphy, there was a shift to the left in the elution profile of IL8-treated r ats, demonstrating the presence of chains with decreased negative charge. n s infusion into rats results in a decreased total negative charge of the HS GAG. Because IL8 has been found in the serum of same patients with minimal lesion nephrotic syndrome, this finding may explain, at least in part, the reported reduced glomerular charge barrier observed in these patients.