Bernard A C, Fitzpatrick E A, Maley M E, Gellin G L, Tsuei B J, Arden W A, Boulanger B R, Kearney P A, Ochoa J B
Vascular and Trauma/Critical Care Research Program, University of Kentucky College of Medicine, Lexington 40536-0298, USA.
Surgery. 2000 Apr;127(4):412-8. doi: 10.1067/msy.2000.104115.
Arginase, which metabolizes L-arginine within the urea cycle, is essential for production of polyamines and affects production of nitric oxide by depletion of L-arginine, the common substrate for both arginase and nitric oxide synthase. Having shown that trauma increases splenic macrophage arginase activity, we seek to define the mechanisms for this. RAW macrophage arginase activity and expression are increased by 8-bromo-cAMP in vitro. We hypothesize that since catecholamines increase cAMP, trauma-induced splenic arginase activity may be mediated by post-injury catecholamine release.
RAW 264.7 macrophage arginase activity was measured in vitro in response to 4 catecholamines with or without propranolol or lipopolysaccharide (LPS). C57BL/6 mice underwent laparotomy as a model of moderate trauma after propranolol treatment, with and without intraperitoneal Escherichia coli LPS administration as a simulated pro-inflammatory stimulus.
Macrophage arginase activity increased in vitro in response to catecholamines or LPS (P < .05). Propranolol pretreatment blocked macrophage arginase activity induced by epinephrine (10 mumol/L) in vitro (P < .05). Trauma or LPS alone increased splenic arginase activity in vivo (P < .05). Propranolol did not alter LPS-induced splenic arginase activity but did significantly reduce trauma-induced splenic arginase activity (P < .05).
Catecholamines alone increase macrophage arginase activity through beta-adrenoceptor activation. Increased splenic arginase activity induced by moderate trauma is decreased by beta-adrenoceptor blockade, suggesting that trauma-induced arginase activity is partly mediated by endogenous catecholamines.
精氨酸酶在尿素循环中代谢L-精氨酸，对多胺的产生至关重要，并通过消耗L-精氨酸影响一氧化氮的产生，L-精氨酸是精氨酸酶和一氧化氮合酶的共同底物。我们已经证明创伤会增加脾脏巨噬细胞精氨酸酶的活性，我们试图确定其机制。在体外，8-溴-cAMP可增加RAW巨噬细胞精氨酸酶的活性和表达。我们假设，由于儿茶酚胺会增加cAMP，创伤诱导的脾脏精氨酸酶活性可能由损伤后儿茶酚胺的释放介导。
在有或没有普萘洛尔或脂多糖（LPS）的情况下，体外测量RAW 264.7巨噬细胞对4种儿茶酚胺的精氨酸酶活性。用普萘洛尔处理后，C57BL/6小鼠接受剖腹手术作为中度创伤模型，有或没有腹腔注射大肠杆菌LPS作为模拟促炎刺激。
巨噬细胞精氨酸酶活性在体外对儿茶酚胺或LPS有反应时增加（P <.05）。普萘洛尔预处理可阻断肾上腺素（10 μmol/L）在体外诱导的巨噬细胞精氨酸酶活性（P <.05）。单独的创伤或LPS会在体内增加脾脏精氨酸酶活性（P <.05）。普萘洛尔不会改变LPS诱导的脾脏精氨酸酶活性，但会显著降低创伤诱导的脾脏精氨酸酶活性（P <.05）。
单独的儿茶酚胺通过β-肾上腺素能受体激活增加巨噬细胞精氨酸酶活性。β-肾上腺素能受体阻断可降低中度创伤诱导的脾脏精氨酸酶活性增加，这表明创伤诱导的精氨酸酶活性部分由内源性儿茶酚胺介导。
