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Article: Skin allograft rejection in mice lacking inducible nitric oxide synthase

TitleSkin allograft rejection in mice lacking inducible nitric oxide synthase
Authors
Issue Date1997
Citation
Transplantation, 1997, v. 64, n. 4, p. 589-593 How to Cite?
AbstractBackground. During allograft rejection, up-regulation of cytokine- inducible nitric oxide synthase (iNOS) leads to the production of large amounts of nitric oxide (NO). The net effect of NO on the alloimmune response is, however, difficult to predict because of its diverse biological effects, which include potentially opposing roles as an effector and immunoregulatory molecule. Methods. In this study, the role of iNOS on the in vitro and in vivo alloimmune response was defined using mutant mice that lack a functional iNOS gene. The ability of spleen cells obtained from iNOS-deficient mutants to proliferate and to produce cytokines in response to irradiated BALB/c stimulator cells was determined, and the rate at which iNOS-deficient mice were able to reject BALB/c skin allografts was observed. Results. Spleen cells from homozygous iNOS-deficient (129xMF1)F1 mice, when compared with cells from heterozygous control mice, showed an increased in vitro proliferative response and produced substantially higher levels of interferon-γ, and also more interleukin-2 and interleukin-12, in response to allogeneic stimulation. The kinetics of BALB/c skin graft rejection were comparable in heterozygous control animals and iNOS-deficient mice. Moreover, no net effect of iNOS on skin allograft rejection was apparent in mice treated with depleting monoclonal antibodies (mAb) to CD4 or CD8 T cells, either alone or in combination, or in mice treated with both anti-CD8 mAb and a neutralizing anti-tumor necrosis factor mAb. Conclusions. These results show that iNOS has an immunomodulatory effect on the in vitro alloimmune response but lack of iNOS has no net influence on the kinetics of murine skin allograft rejection in either unmodified recipients or recipients in which the early contribution of T-cell subsets and tumor necrosis factor-α to graft rejection has been abrogated.
Persistent Identifierhttp://hdl.handle.net/10722/200059
ISSN
2015 Impact Factor: 3.69
2015 SCImago Journal Rankings: 1.699
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCasey, John J.-
dc.contributor.authorWei, Xiaoqing-
dc.contributor.authorOrr, Douglas J A-
dc.contributor.authorAlastair Gracie, J.-
dc.contributor.authorHuang, Fangping-
dc.contributor.authorBolton, Eleanor Mary-
dc.contributor.authorLiew, Fooyew-
dc.contributor.authorAndrew Bradley, J.-
dc.date.accessioned2014-07-26T23:11:05Z-
dc.date.available2014-07-26T23:11:05Z-
dc.date.issued1997-
dc.identifier.citationTransplantation, 1997, v. 64, n. 4, p. 589-593-
dc.identifier.issn0041-1337-
dc.identifier.urihttp://hdl.handle.net/10722/200059-
dc.description.abstractBackground. During allograft rejection, up-regulation of cytokine- inducible nitric oxide synthase (iNOS) leads to the production of large amounts of nitric oxide (NO). The net effect of NO on the alloimmune response is, however, difficult to predict because of its diverse biological effects, which include potentially opposing roles as an effector and immunoregulatory molecule. Methods. In this study, the role of iNOS on the in vitro and in vivo alloimmune response was defined using mutant mice that lack a functional iNOS gene. The ability of spleen cells obtained from iNOS-deficient mutants to proliferate and to produce cytokines in response to irradiated BALB/c stimulator cells was determined, and the rate at which iNOS-deficient mice were able to reject BALB/c skin allografts was observed. Results. Spleen cells from homozygous iNOS-deficient (129xMF1)F1 mice, when compared with cells from heterozygous control mice, showed an increased in vitro proliferative response and produced substantially higher levels of interferon-γ, and also more interleukin-2 and interleukin-12, in response to allogeneic stimulation. The kinetics of BALB/c skin graft rejection were comparable in heterozygous control animals and iNOS-deficient mice. Moreover, no net effect of iNOS on skin allograft rejection was apparent in mice treated with depleting monoclonal antibodies (mAb) to CD4 or CD8 T cells, either alone or in combination, or in mice treated with both anti-CD8 mAb and a neutralizing anti-tumor necrosis factor mAb. Conclusions. These results show that iNOS has an immunomodulatory effect on the in vitro alloimmune response but lack of iNOS has no net influence on the kinetics of murine skin allograft rejection in either unmodified recipients or recipients in which the early contribution of T-cell subsets and tumor necrosis factor-α to graft rejection has been abrogated.-
dc.languageeng-
dc.relation.ispartofTransplantation-
dc.titleSkin allograft rejection in mice lacking inducible nitric oxide synthase-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/00007890-199708270-00007-
dc.identifier.pmid9293870-
dc.identifier.scopuseid_2-s2.0-0030929522-
dc.identifier.volume64-
dc.identifier.issue4-
dc.identifier.spage589-
dc.identifier.epage593-
dc.identifier.isiWOS:A1997XU04800007-

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