L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines 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 interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

Cytomegalovirus detection in kidney transplants: results obtained from the polymerase chain reaction.

Kidneys from twelve renal transplant recipients were examined prior to and after graft failure and explantation. The investigations included conventional light and electron microscopy and the analysis of human cytomegalovirus-related viral proteins and viral DNA. Nucleic acid hybridization studies were conducted on kidney explants by an in situ method using DNA probes and by the polymerase chain reaction employing primers and probe for immediate early gene targets. In none of the cases did light and electron microscopy including immunohistochemistry for human cytomegalovirus reveal active infection in punch biopsies or explants. Interestingly, in situ hybridization also failed to detect human cytomegalovirus even in two cases with seroconversion, while the polymerase chain reaction was positive. The polymerase chain reaction disclosed only two additional positive cases within the residual group of explanted kidneys. In our hands, the polymerase chain reaction was the only potent direct detection method for cytomegalovirus in transplanted human kidneys.