Angiotensin II regulatesthe radical production of polymorphonuclearleukocytes: Evidence in Angiotensi II type 1a receptor knockout mice

目的虽然血管紧张素II（AII）与其对细胞因子或趋化因子的炎症和氧化作用有关，但关于AII对多形粒细胞（PMN）的吞噬功能尚不清楚。我们评估了AII在活性氧（ROS）和一氧化氮（NO）中的作用。方法采用流式细胞仪检测碘化丙啶标记的S.金黄色葡萄球菌或佛波醇肉豆蔻酸酯乙酸酯（PMA）（25 μg/ml）。我们测试了5组的PMN：C57 BL/6野生型小鼠（C组）、AII 1A型受体敲除小鼠（KO组）、C57 BL/6小鼠暴露于AII（1000 ng/kg/min皮下注射）（A组）或生理盐水（S组）2周以及C57 BL/6小鼠给予AII受体阻断剂氯沙坦（100 mg/L饮用水）2周（L组）。动物的体重或PMN计数无差异。结果PMA刺激后A组细胞产生的ROS明显高于其他各组。吞噬刺激的ROS产生量A组也高于C组。KO组基础水平ROS生成量低于其他组。在KO组中，在基础和吞噬细胞刺激时的NO产生均低于其他组。甚至在KO组中也观察到PMA或吞噬作用刺激的自由基产生。结论Ang Ⅱ通过吞噬和PMA刺激两种途径刺激PLM产生ROS。在Ang Ⅱ慢性刺激下，吞噬刺激后NO的产生没有变化。

Objective Although angiotensin II (AII) has been linked to its inflammatory and oxidative effects on cytokine or chemokine, little is known about the phagocytic function of AII on polymorphonuclear leulocytes (PMN). We evaluate the role of AII in reactive oxygen species (ROS) and of nitric oxide (NO). Methods Using flow cytometry, we compared the ROS production of PMN after (propidium iodide-labeled) S. aureus or phorbol myristate acetate (PMA) (25 μg/ml). We tested the PMN from the 5 groups: C57BL/6 wild type mice (Group C), AII type 1A receptor knock-out mice (Group KO), C57BL/6 mice exposed to either AII (1000 ng/kg per minute subcutaneously) (Group A) or saline (Group S) for 2 weeks, and C57BL/6 mice administrated AII receptor blocker, losartan (100mg/L drinking water) for 2 weeks (Group L). Animals did not differ in body weight or PMN counts. Results ROS production stimulated by PMA was higher in the group A than in other groups. ROS production stimulated by phagocytosis was also higher in the group A than in group C. ROS production at basal in group KO was lower than other groups. In the group KO, NO production both at basal and phagocytic stimulation was lower than in other groups. The radical production stimulated by PMA or phagocytosis was observed even in the Group KO. Conclusions Ang II stimulated the ROS production of PLM both by phagocytosis and PMA stimulation. Under the chronic stimulation with Ang II, NO production was not changed after the stimulation of phagocytosis.