Munder Markus, Mollinedo Faustino, Calafat Jero, Canchado Javier, Gil-Lamaignere Cristina, Fuentes José M, Luckner Claudia, Doschko Gwendolyn, Soler Germán, Eichmann Klaus, Müller Frank-Michael, Ho Anthony D, Goerner Martin, Modolell Manuel
Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Blood. 2005 Mar 15;105(6):2549-56. doi: 10.1182/blood-2004-07-2521. Epub 2004 Nov 16.
The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro. We demonstrate that arginase I is localized in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome. Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase.
通过一氧化氮合酶(NOS)或精氨酸酶进行的精氨酸代谢平衡是小鼠巨噬细胞和树突状细胞炎症反应的重要决定因素。在此,我们分析了人髓细胞中精氨酸酶I同工型的表达。利用健康供体和精氨酸酶I缺乏症患者,我们发现人白细胞中的精氨酸酶I仅在粒细胞中组成性表达,并且在体外不受多种促炎和抗炎刺激的调节。我们证明精氨酸酶I定位于中性粒细胞的嗜天青颗粒中,并构成一种新的抗菌效应途径,可能是通过吞噬溶酶体中的精氨酸耗竭来实现的。我们的研究结果表明,在通过精氨酸酶进行的精氨酸代谢的调节和功能方面,小鼠和人白细胞之间存在重要差异。