title: Phagocyte-derived catecholamines enhance acute inflammatory injury.
abstract: It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Flierl
authors.forename: Daniel
authors.initials: D
authors.lastname: Rittirsch
authors.forename: Brian A
authors.initials: BA
authors.lastname: Nadeau
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Chen
authors.forename: J Vidya
authors.initials: JV
authors.lastname: Sarma
authors.forename: Firas S
authors.initials: FS
authors.lastname: Zetoune
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: McGuire
authors.forename: Rachel P
authors.initials: RP
authors.lastname: List
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Day
authors.forename: L Marco
authors.initials: LM
authors.lastname: Hoesel
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Markus S
authors.initials: MS
authors.lastname: Huber-Lang
authors.forename: Richard R
authors.initials: RR
authors.lastname: Neubig
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000208:Acute Disease; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D002395:Catecholamines; D008070:Lipopolysaccharides; D018341:Receptors, Adrenergic, alpha-2