Abstract
AIM: To evaluate the immunologic role and expression significances of nitric oxide (NO), nitric oxide synthase (NOS), and its isoenzyme in acute rejection to liver xenografts from golden hamster in rat.
METHODS: Liver transplantations were randomly divided into five groups (n = 6-9):isografts (group I); xenografts (group II); xenografts plus cyclosporine treatment (group III), xenografts plus cyclophosphamide treatment combined with splenectomy (group IV), and xenografts using cyclophosphamide in combination with splenectomy (group IV) and xenografts using splenectomy in addition to cyclophosphamide and cyclosporine treatments (group V). The levels of ALT, TNF-α, and nitric oxide production (NOx) in serum of reciprents were examined, and expressions of type II (iNOS) and type III (cNOS) nitric oxide synthase (NOS)-inducible NOS (iNOS) and constitutive NOS (cNOS) were observed by NADPH diaphorase histochemical and immunohistochemical staining.
RESULTS: The level of serum ALT, activity of serum TNF-α and systemic levels of NO metabolite in groups II and IV were higher than those of groups I and V (serum ALT, 2416 ± 475, 2540 ± 82.5) nkat•L⁻¹-1vs (556.8 ± 43.5, 677.30 ± 38.2) nkat•L⁻¹-1, P < 0.01; (serum TNF-α, 353.5 ± 16.1, 444.6 ± 28.1) ng•L-1, vs 38.5 ± 5.2, 52.0 ± 5.7) ng•L-1, P < 0.01; (serum NOx 514.6 ± 18.1, 336.0 ± 43.0) nmol•g⁻¹, vs 26.1 ± 5.7, 27.7 ± 6.0) nmol•g⁻¹, P < 0.01. Cyclosporine in group III can repress the cellular immune response and the synthesis of nitric oxide and the expression of NO synthase, but not prolong the liver xenograft survival. The over-expression of NOS, iNOS and cNOS in liver xenograft rejection in groups II and IV were detected by NADPH diaphorase histochemical and immunohistochemical staining.
CONCLUSION: The degrees of acute rejection can be effectively repressed in golden hamster to rat liver xenografts with splenectomy and cyclosporine. Nitric oxide metabolites, and nitric oxide synthase and its isoenzymes, above all inducible NOS (iNOS) can be used as potential diagnostic markers for acute rejection in liver transplantation. The cellular localization of nitric oxide varies according to the immunologic status of liver xenografts, thus thinking that hepatocyte derived nitric oxide may be protective in the hyporesponsive state, but hepatic injury is likely triggered by centrilobular iNOS expression in the superresponsive state.
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