Beta adrenoceptor regulation of macrophage arginase activity

Background. Arginase, which metabolizes L-arginine within the urea cycle, i s essential for production of polyamines and affects production of nitric o xide by depletion of L-arginine, the common substrate for both arginase and nitric oxide synthase. Having shown that trauma increases splenic macropha ge arginase activity, we seek to define the mechanisms for this. RAW macrop hage arginase activity and expression are increased by 8-bromo-cAMP in vitr o. We hypothesize that since catecholamines increase cAMP, trauma-induced s plenic arginase activity may be mediated by post-injury catecholamine relea se. Methods. RAW 264.7 macrophage arginase activity runs measured in vitro in r esponse to 4 catecholamines with or without propranolol or lipopolysacchari de (LPS). C57BL/6 mice underwent laparotomy as a model of moderate trauma a fter propranolol treatment, with and without intraperitoneal Escherichia co li LPS administration as a simulated pro-inflammatory stimulus. Results. Macrophage arginase activity increased in vitro in response to cat echolamines or LPS (P < .05). Propranolol pretreat ment blocked macrophage arginase activity induced by epinephrine (10 mu mol/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 sig nificantly reduce trauma-induced splenic arginase activity (P < .05). Conclusions. Catecholamines alone increase macrophage arginase activity thr ough beta-adrenoceptor activation. Increased splenic arginase activity indu ced by moderate trauma is decreased by beta-adrenoceptor blockade, suggesti ng that trauma-induced arginase activity is partly mediated by endogenous c atecholamines.