title: Beta adrenoceptor regulation of macrophage arginase activity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Vascular and Trauma/Critical Care Research Program, University of Kentucky College of Medicine, Lexington 40536-0298, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Bernard
authors.forename: E A
authors.initials: EA
authors.lastname: Fitzpatrick
authors.forename: M E
authors.initials: ME
authors.lastname: Maley
authors.forename: G L
authors.initials: GL
authors.lastname: Gellin
authors.forename: B J
authors.initials: BJ
authors.lastname: Tsuei
authors.forename: W A
authors.initials: WA
authors.lastname: Arden
authors.forename: B R
authors.initials: BR
authors.lastname: Boulanger
authors.forename: P A
authors.initials: PA
authors.lastname: Kearney
authors.forename: J B
authors.initials: JB
authors.lastname: Ochoa
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D004790:Enzyme Induction; D004837:Epinephrine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D007813:Laparotomy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology; D014947:Wounds and Injuries / Q000201:enzymology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008070:Lipopolysaccharides; D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011433:Propranolol; D001119:Arginase; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine