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Production of nitric oxide during graft rejection is regulated by the Th1/Th2 balance, the arginase activity, and L-arginine metabolism

, : Production of nitric oxide during graft rejection is regulated by the Th1/Th2 balance, the arginase activity, and L-arginine metabolism. Transplantation 81(12): 1708-1715

Background. Production of nitric oxide (NO) by graft infiltrating macrophages has been proposed as an important effector mechanism of allograft rejection. Although high levels of NO are generated during allograft rejection, undetectable or only limited amounts of NO were found in rejected skin xenografts.Methods. BALB/c mice were grafted with skin transplants from syngeneic, allogeneic or xenogeneic (rat) donors. The production of NO, cytokines and arginase in the grafts was determined by spectrophotometry, enzyme-linked immunosorbent assay, or polymerase chain reaction. Effects of depletion of CD4(+) cells, neutralization of interleukin (IL)-4 or application of arginase inhibitors N-omega-hydroxy-L-arginine (L-NOHA) and L-valine on production of NO in rejected xenografts were evaluated.Results. Rejection of rat skin xenografts, on the contrary to rejection of allografts, was associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of arginase genes, strongly enhanced arginase activity and attenuated NO generation in the graft. The supernatants obtained after cultivation of skin xenograft (but not allograft or syngeneic graft) explants contained a high arginase activity and strongly suppressed NO production by activated macrophages. This suppression was completely inhibited by L-NOHA or was overcome by an excess of exogenous L-arginine, a substrate for NO synthesis. Cocultivation of xenograft explants that did not produce NO with arginase inhibitors L-NOHA or L-valine restored NO generation in the graft.Conclusion. The results suggest that upregulation of arginase activity by Th2 cytokines during xenograft rejection limits the bioavailability of L-arginine for the inducible NO synthase and thus attenuates generation of NO by the graft-infiltrating macrophages.


PMID: 16794538

DOI: 10.1097/

Other references

Angelico, M.; Mangiameli, A.; Della Guardia, P.; Sofia, M.; Nistri, A.; Maina, M.; Baiocchi, L.; Blasi, A., 1993: N-Ethyltauroursodeoxycholic acid, an amidated bile salt analogue resistant to deconjugation Metabolism and bile secretory properties after duodenal infusion in the rat. Hepatology 18(4 PART 2): 178A

Anonymous, 1940: The Prevention of Adhesions. Canadian Medical Association Journal 42(6): 578-578

Hachemaoui, M.; Ris, L.; Vibert, N.; Godaux, E.; Vidal, P.P.; Moore, L.E., 2001: Spectral analysis of spike discharge of the guinea pig medial vestibular nucleus. The second-order relay neurons of the medial vestibular nucleus show spontaneous firing behavior in vitro, with rates ranging from below 1 Hz to 40-50 Hz. We have shown previously that effective modulation is possible for rates above 10 Hz, howeve...

Wang, K.S.; Schmaljohn, A.L.; Kuhn, R.J.; Strauss, J.H., 1991: Antiidiotypic antibodies as probes for the Sindbis virus receptor. Rabbit polyclonal antiidiotypic antibodies were made to mouse monoclonal antibodies that neutralize the infectivity of Sindbis virus. One of the antiidiotypic antisera obtained has properties characteristic of an antireceptor antiserum. It binds t...

Steffens, J.J.; Siewers, I.J.; Benkovic, S.J., 1975: Catalysis of phosphoryl group transfer. The role of divalent metal ions in the hydrolysis of lactic acid O-phenyl phosphate and salicylic acid O-aryl phosphates. The spontaneous hydrolyses of lactic acid O-phenyl phosphate (I) and, to a lesser extent, 3-hydroxybutyric acid O-phenyl phosphate (II) have been investigated and compared with similar intramolecular and bimolecular reactions. Compared to bimolecu...

Koller, W.C.; Cochran, J.W.; Klawans, H.L., 1979: Calcification of the basal ganglia: computerized tomography and clinical correlation. During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral i...

Dimri, D.; Sethi, B.; Kumar, Y., 2012: De novo histoid leprosy in an elderly: a case report and review of the literature. Histoid leprosy, an uncommon variant of lepromatous leprosy, develops usually as relapse in lepromatous patients who are on dapsone monotherapy, but uncommonly arises de novo. This rare form of the disease, with unique clinical and histopathologic...

Mclaughlin, T.J.; Gurwitz, J.; Gao, X.; Soumerai, S.B., 1997: Delayed thrombolysis in patients with acute myocardial infarction. Jgim 12(Suppl 1): 76

Chen, Y.; Taghian, A.; Goldberg, S.; Assaad, S.; Abi Raad, R.; Michaelson, J.; Powell, S., 2003: Influence of margin status and tumor bed boost dose on local recurrence rate in breast-conserving therapy Does a higher radiation dose to the tumor bed overcome the effect of close or positive margin status in breast-conserving therapy?. International Journal of Radiation Oncology Biology Physics 57(2 Supplement): S358

Gin Thon T.; Grandy George A.; Loer Robert F., 1964: Lithology, mineralogy, and magnetic concentration characteristics of the Atlantic City iron formation. Mining Engineering 16(12): 89