Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
J Leukoc Biol. 2010 Jun;87(6):1125-32. doi: 10.1189/jlb.1109741. Epub 2010 Mar 3.
Human polymorphonuclear PMN constitutively express the enzyme arginase I, which hydrolyzes arginine to ornithine and urea. This arginine consumption has been recognized as a key pathway of myeloid cell-mediated suppression of the adaptive immune system during inflammation, infection, and tumor growth. Eos granulocytes are crucial immunoregulatory and effector cells of allergic inflammation and infections with parasites and helminths and in a variety of tumors. Here, we analyzed if human Eos also express arginase with its potential immunosuppressive consequences. We show that human peripheral blood Eos do not express arginase I or II protein or arginase enzymatic activity. Correspondingly, no metabolism of arginine to ornithine can be detected in Eos-S. Neither Eos apoptosis nor cytokine-mediated cellular activation induces arginase in human Eos in vitro. Finally, we show that arginase activity and protein are also undetectable in Eos of allergic patients from peripheral blood or from BALF activated in vivo during allergic pulmonary inflammation. This work demonstrates a fundamental difference between neutrophil and Eos granulocytes. As Eos are not equipped with the immunosuppressive enzyme arginase, they cannot participate, via arginine limitation, in the suppression of the evolving adaptive immune response in allergy, infections, or tumor immunity.
人类多形核粒细胞 PMN 持续表达酶精氨酸酶 I，它将精氨酸水解为鸟氨酸和尿素。这种精氨酸消耗被认为是髓样细胞在炎症、感染和肿瘤生长过程中抑制适应性免疫系统的关键途径。嗜酸性粒细胞是过敏炎症和寄生虫及蠕虫感染以及各种肿瘤中至关重要的免疫调节和效应细胞。在这里，我们分析了人类嗜酸性粒细胞是否也表达具有潜在免疫抑制作用的精氨酸酶。我们发现，人外周血嗜酸性粒细胞不表达精氨酸酶 I 或 II 蛋白或精氨酸酶酶活性。相应地，在嗜酸性粒细胞中不能检测到精氨酸向鸟氨酸的代谢。人嗜酸性粒细胞在体外凋亡或细胞因子介导的细胞激活也不会诱导精氨酸酶。最后，我们发现，在过敏性肺部炎症期间，来自外周血或 BALF 的过敏性患者的嗜酸性粒细胞中，也无法检测到精氨酸酶活性和蛋白。这项工作表明中性粒细胞和嗜酸性粒细胞之间存在根本差异。由于嗜酸性粒细胞没有配备免疫抑制酶精氨酸酶，因此它们不能通过精氨酸限制参与过敏、感染或肿瘤免疫中适应性免疫反应的抑制。
