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.
Haberstroh
U
U
Department of Internal Medicine, University Hospital Eppendorf, Hamburg, Germany.
Stilo
K
K
Pocock
J
J
Wolf
G
G
Helmchen
U
U
Wenzel
U
U
Zahner
G
G
Stahl
R A
RA
Thaiss
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D001120:Arginine / Q000494:pharmacology*; D015152:Blotting, Northern; D018946:Chemokine CCL5 / Q000032:analysis / Q000096:biosynthesis*; D002633:Chemotaxis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000033:anatomy & histology / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D018946:Chemokine CCL5; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester