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Br J Pharmacol. 2009 Oct;158(3):638-51. doi: 10.1111/j.1476-5381.2009.00291.x. Epub 2009 Sep 17.

Arginase: an emerging key player in the mammalian immune system.

Author information

1
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany. Markus_Munder@med.uni-heidelberg.de

Abstract

The enzyme arginase metabolizes L-arginine to L-ornithine and urea. Besides its fundamental role in the hepatic urea cycle, arginase is also expressed the immune system of mice and man. While significant interspecies differences exist regarding expression, subcellular localization and regulation of immune cell arginase, associated pathways of immunopathology are comparable between species. Arginase is induced in murine myeloid cells mainly by Th2 cytokines and inflammatory agents and participates in a variety of inflammatory diseases by down-regulation of nitric oxide synthesis, induction of fibrosis and tissue regeneration. In humans, arginase I is constitutively expressed in polymorphonuclear neutrophils and is liberated during inflammation. Myeloid cell arginase-mediated L-arginine depletion profoundly suppresses T cell immune responses and this has emerged as a fundamental mechanism of inflammation-associated immunosuppression. Pharmacological interference with L-arginine metabolism is a novel promising strategy in the treatment of cancer, autoimmunity or unwanted immune deviation.

PMID:
19764983
PMCID:
PMC2765586
DOI:
10.1111/j.1476-5381.2009.00291.x
[Indexed for MEDLINE]
Free PMC Article

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