Effects of catecholamines on kinase activation in lung neutrophils after hemorrhage or endotoxemia

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Abstract
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.
Funding Information
  • National Institutes of Health (HL 62221)