Effects of catecholamines on kinase activation in lung neutrophils after hemorrhage or endotoxemia.
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 alpha- or beta-antagonists or alpha-adrenergic agonists before hemorrhage or endotoxemia. These studies showed that alpha-, but not beta-adrenergic stimuli, modulated the severity of acute lung injury after hemorrhage or endotoxemia, and alpha-adrenergic stimuli was proinflammatory after hemorrhage but anti-inflammatory after endotoxemia. The observed alpha-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 alpha- or beta-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.
Arcaroli
John
J
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Yang
Kuang-Yao
KY
Yum
Ho-Kee
HK
Kupfner
John
J
Pitts
Todd M
TM
Park
Jong Sung
JS
Strassheim
Derek
D
Abraham
Edward
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects; D006470:Hemorrhage / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D009195:Peroxidase / Q000032:analysis; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011810:Quinoxalines; D010656:Phenylephrine; D000068438:Brimonidine Tartrate; D011433:Propranolol; D009195:Peroxidase; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019893:Ribosomal Protein S6 Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras); D010646:Phentolamine