ABSTRACT
Ischemia-reperfusion injury (IRI) is a non-specific, antigen independent event, which significantly influences the outcome of transplanted organs. Interleukin-4 (IL-4) is an immunological mediator belonging to the interleukin family that mainly regulates the differentiation of T-helper lymphocytes into Th2 phenotype as well as enhances cellular activation, both are important features in IRI. The influence of polyclonal antithymocyte globulins (ATGs) on expression of IL-4 in reperfused tissues of cynomolgus monkeys (n=18) after 60 min of ischemia was assessed by immunohistochemical methods. Our results show an inhibition of the production and release of IL-4 by activated lymphocytes in the groups treated with ATGs in comparison to control, although a causal relationship between IL-4 and tissue damage was not demonstrated. Implication of IL-4 as an inflammatory mediator upon IRI must be further investigated.
Subject(s)
Antilymphocyte Serum/pharmacology , Interleukin-4/metabolism , Reperfusion Injury/immunology , T-Lymphocytes/immunology , Animals , Extremities/blood supply , Interleukin-4/analysis , Interleukin-4/immunology , Leukocyte Common Antigens/analysis , Macaca fascicularis , Muscle, Skeletal/blood supply , Muscle, Skeletal/chemistry , PrimatesABSTRACT
Reactive oxygen and nitrogen species have been implicated in the pathogenesis of asbestos fibers-associated pulmonary diseases. By comparing the responses of inducible nitric oxide synthase (iNOS) knockout and wild-type mice we investigated the consequences of iNOS expression for the development of the inflammatory response and tissue injury upon intratracheal instillation of asbestos fibers. Exposure to asbestos fibers resulted in an increased iNOS mRNA and protein expression in the lungs from wild-type mice. Moreover, iNOS knockout mice exhibited an exceeded pulmonary expression and production of TNF-alpha as well as a higher influx of neutrophils into the alveolar space than wild-type mice. In contrast, iNOS knockout animals displayed an attenuated oxidant-related tissue injury reflected in a decrease in protein leakage and LDH release into the alveolar space as well as weaker nitrotyrosine staining of lung tissue compared to wild-type mice. Data presented here indicate that iNOS-derived NO exerts a dichotomous role in acute asbestos-induced lung injury in that iNOS deficiency resulted in an exacerbated inflammatory response but improved oxidant-promoted lung tissue damage.
