Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase
Autor: | Joseph R. Williamson, Ronald G. Tilton, W. D. Lazenby, T. P. Misko, Pamela T. Manning, Tien-Sung Lin, N. K. Worrall, T. B. Ferguson, C P Rodi |
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Rok vydání: | 1995 |
Předmět: |
Graft Rejection
medicine.medical_treatment Molecular Sequence Data Immunology Gene Expression Pharmacology Nitric Oxide Guanidines Nitric oxide chemistry.chemical_compound Immune system In vivo medicine Animals Immunology and Allergy Amino Acid Sequence RNA Messenger Enzyme inducer DNA Primers Heart transplantation Base Sequence biology Articles medicine.disease Molecular biology Pimagedine Rats Rats Inbred ACI Transplant rejection Nitric oxide synthase chemistry Rats Inbred Lew Enzyme Induction biology.protein Heart Transplantation Amino Acid Oxidoreductases Nitric Oxide Synthase |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
Popis: | The role of nitric oxide in the immune response to allogeneic tissue was explored in an in vivo cardiac transplant model in the rat. Nitric oxide production during organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the inducible nitric oxide synthase enzyme was detected in the rejecting allografted heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated to be biologically active by the in vitro conversion of L-arginine to L-citrulline and was immunohistochemically localized to the infiltrating inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, prevented the increased nitric oxide production in the transplanted organ and significantly attenuated the pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection. These results suggest an important role for nitric oxide in mediating the immune response to allogeneic tissue. Inhibition of inducible nitric oxide synthase may provide a novel therapeutic modality in the management of acute transplant rejection and of other immune-mediated processes. |
Databáze: | OpenAIRE |
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