L-ARGININE SUPPRESSES LIPOPOLYSACCHARIDE-INDUCED EXPRESSION OF RANTESIN GLOMERULI

Endotoxemia leads to the infiltration of inflammatory cells in glomeru li and the tubulointerstitium of the kidney. The ultimate mechanisms f or this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activ ation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemok ines might play in the regulation of this inflammatory cell infiltrate . Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interacti ons between the chemokine RANTES and the L-arginine/NO pathway. To ind uce endotoxemia, rats were injected intraperitoneally with lipopolysac charide (LPS). Glomeruli were isolated over a 24-h time period, and RA NTES was assessed by Northern blotting, a chemotactic assay, and a spe cific enzyme-linked immunosorbent assay. The chemokine release was ass ociated with increased glomerular infiltration of monocytes/macrophage s. LPS also stimulated the mRNA expression of inducible NO synthase an d increased the release of nitrite into the supernatants of isolated g lomeruli. Supplementation of L-arginine intake increased the release o f glomerular nitrite and reduced glomerular RANTES expression after th e injection of LPS. Inhibition of the L-arginine/NO pathway by the uns pecific NO synthase inhibitor N-G-nitro-L-arginine methylester signifi cantly increased glomerular RANTES mRNA expression and the number of i nfiltrating glomerular macrophages. These data demonstrate that L-agin ine suppresses glomerular RANTES formation and suggest that the chemok ine-mediated recruitment of glomerular macrophages in LPS-induced endo toxemia can be modulated by the L-arginine/NO pathway.