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Effects of catecholamines on kinase activation in lung neutrophils after hemorrhage or endotoxemia
Author(s) -
Arcaroli John,
Yang KuangYao,
Yum HoKee,
Kupfner John,
Pitts Todd M.,
Park Jong Sung,
Strassheim Derek,
Abraham Edward
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.3.571
Subject(s) - proinflammatory cytokine , kinase , p38 mitogen activated protein kinases , protein kinase a , biology , immune system , lung , signal transduction , inflammation , adrenergic , pharmacology , immunology , medicine , endocrinology , receptor , microbiology and biotechnology
Catecholamines are released in high levels after hemorrhage or endotoxemia and have been shown to modulate immune function, including cellular release of inflammatory mediators. In the present experiments, we examined the effects of endogenous and exogenous catecholamines on neutrophil accumulation and activation in the lungs using pretreatment with α‐ or β‐antagonists or α‐adrenergic agonists before hemorrhage or endotoxemia. These studies showed that α‐, but not β‐adrenergic stimuli, modulated the severity of acute lung injury after hemorrhage or endotoxemia, and α‐adrenergic stimuli was proinflammatory after hemorrhage but anti‐inflammatory after endotoxemia. The observed α‐adrenergic effects on lung neutrophil activation appeared to involve primarily the extracellular signal‐regulated kinase pathway at the upstream kinase Raf, but not Ras. Although p38 and protein kinase A were activated in lung neutrophils after hemorrhage or endotoxemia, these kinases were not affected by α‐ or β‐adrenergic modulation. These results demonstrate that catecholamines have important immunomodulatory effects in vivo that affect intracellular signaling pathways in neutrophils and neutrophil‐driven, inflammatory processes such as the development of acute lung injury.