Role of cytokine in inflammatory response.
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概要
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There is a considerable body of evidence that inflammatory response is mediated by various cytokines. IL-5 is one of inflammatory cytokines. The study of IL-5 has been originated in the search for one of the B cell growth and differentiation factors, named T cell-replacing factor (TRF), that induces antigen-stimulated B cells to differentiate into plasma cells. Eosinophil differentiation factor (EDF) has been known as a diffusible factor from thoracic duct lymphocytes of parasite-infected rats. The cDNA cloning and mAb against IL-5 enable us to identify this molecule as a cytokine (TRF/EDF) that has pleiotropic activity <I>in vitro</I> on various target cells besides B cells and eosinophils. The IL-5 transgenic mice show not only polyclonal B cell activation represented by enhanced serum levels of IgM, IgA, and IgE and autoantibody production, but also massive eosinophilia in peripheral blood and eosinophil infiltration into various tissues.<BR>The pleiotropic activity of IL-5 on target cells is directly dependent on initial binding to specific cell-surface receptor (IL-5R) . IL-5 interacts with target cells with biphasic equilibrium binding kinetics, reflecting two classes of binding sites with high and low affinity. We carried out the cloning of the cDNA for the IL-5Rα chain which found IL-5 with low affinity by itself. The IL-5Rα chain associates with the β chain which can convert low affinity IL-5R to the high affinity. The β chain of IL-5R, that does not bind either IL-5, IL-3, or GM-CSF by itself is shared among IL-5R, IL-3R, and GM-CSFR.<BR>These results can imply why IL-5, IL-3, and GM-CSF are eosinophil-poietin, but can not explain why IL-5 preferentially induces eosinophil production. IL-5 specific signalling may be transduced through IL-5Rα chain. We need further experimentation to give definite answer on these issues.
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