Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany.
Br J Pharmacol. 2009 Oct;158(3):638-51. doi: 10.1111/j.1476-5381.2009.00291.x. Epub 2009 Sep 17.
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.
酶精氨酸酶将 L-精氨酸代谢为 L-鸟氨酸和尿素。除了在肝脏尿素循环中的基本作用外，精氨酸酶还在小鼠和人类的免疫系统中表达。虽然免疫细胞精氨酸酶的表达、亚细胞定位和调节存在显著的种间差异，但物种间的免疫病理学相关途径是可比的。精氨酸酶在小鼠髓样细胞中主要由 Th2 细胞因子和炎症因子诱导，并通过下调一氧化氮合成、诱导纤维化和组织再生，参与多种炎症性疾病。在人类中，Ⅰ型精氨酸酶在多形核粒细胞中组成性表达，并在炎症期间释放。髓样细胞精氨酸酶介导的 L-精氨酸耗竭可显著抑制 T 细胞免疫反应，这已成为炎症相关免疫抑制的一个基本机制。药物干预 L-精氨酸代谢是治疗癌症、自身免疫或免疫偏离的一种有前途的新策略。
