Role of arginine metabolism in immunity and immunopathology
Posted by ~Ray @ 2008-01-01 21:18:27
Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses powerful immunosuppression is also mediated by a subset of myeloid cells that register the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2) which generates nitric oxide (NO) and arginase 1 (Arg1) which depletes the milieu of arginine. Th1 cytokines induce NOS2 whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together peroxynitrites generated by NOS2 under conditions of limiting arginine cause activated T lymphocytes to undergo apoptosis. Thus. NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the back up in a series on the regulation of the immune system by metabolic pathways.
During progression tumors become refractory to the offensive weapons of the immune system. It has been known for a long time that the tumor microenvironment presents a profound modification in the metabolism of arachidonic acid and amino acids such as l-triptophan and l-arginine. However only in the last decade we have started to appreciate how these changes might create dysfunctions in cells of both adaptive and innate immune system. The knowledge of these complex and partially interconnected metabolic pathways is offering new targets for an integrated pharmacological approach aiming at freeing tumor-specific T lymphocytes from the latches of cancer influence.
A heterogeneous set of cells that are commonly grouped as “myeloid cells” interacts in a complex landscape of physiological and pathological situations. In this analyse we attempt to analyse a compose of the “myeloid connection” through different normal and pathological states by analyzing common metabolic pathways of the amino acid l-arginine. Myeloid cells exert various often divergent actions on the immune response through mechanisms that exploit mediators of this peculiar metabolic pathway ranging from.[ADVERTHERE]Related article:
http://www.sciencedirect.com/science?_ob=GatewayURL&_origin=IRSSSEARCH&_method=citationSearch&_piikey=S0171298507001131&_version=1&md5=21f377bbd4187a69a993e7f16d74e752
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