Modulating effects of L-arginine on cytokine-stimulated lymphocyte migration in vitro.
Elective microsurgical transplants have become routine. Yet there remains a 1-5% rate of complete flap necrosis among these surgical reconstructions. This rate is much higher in emergent replantations. Despite technically accurate surgery, perfusion fails in this group. This lack of perfusion, or no-reflow, has been attributed to ischemic-reperfusion injury. The exact nature of this phenomenon remains poorly characterized, though it is clear that significant changes occur in such situations at the endothelial vascular interface. In an effort to understand the biomolecular events involved in ischemic-reperfusion injury we investigated the modulation of leukocyte transendothelial migration. Using a chemotactic chamber model with a cytokine stimulate mono-layer of umbilical vein endothelium, we evaluated the migration rate of peripheral blood mononuclear cells in the presence of exogenous L-arginine and/or the nitric oxide synthase inhibitor L-NAME. Levels of INF-gamma and TNF-alpha production were also determined. It was found that in the face of cytokine pre-stimulation and L-arginine, mononuclear cell trans-endothelial migration increased dramatically. There were also parallel increases in inflammatory cytokine output. These responses were sharply decreased by L-NAME. The results of this study suggest that in vitro nitric oxide augments transendothelial migration of inflammatory cells. Modulation of this response may provide a clinically useful method of minimizing ischemic-reperfusion injury.
Scott Isenberg
J
J
Department of Oral and Maxillofacial Surgery, University of Oklahoma, Norman, OK, USA. jbi2@georgetown.edu
D001120:Arginine / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014471:Umbilical Veins / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester