Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-κB

摘要: Neutrophils are mobilized to the vascular wall during vessel inflammation. Published data conflicting on phagocytic nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activation hypertensive state, and capacity of angiotensin II (Ang II) modulate intracellular redox status has not been analyzed in neutrophils. We here describe that Ang highly stimulates endogenous extracellular O2 production these cells, consistent with translocation cell membrane cytosolic components NADPH oxidase, p47phox, p67phox. The II‐dependent was suppressed by specific inhibitors AT1 receptors, p38MAPK ERK1/2 pathways, flavin oxidases. Furthermore, induced a robust phosphorylation p38MAPK, ERK1/2, JNK1/2 (particularly JNK2), which hindered tyrosine kinases, ROS scavengers. increased Ca2 levels—released mainly from calcium stores—enhanced synthesis de novo activity calcineurin, stimulated DNA-binding transcription factor NF-B cultured human Present demonstrate for first time stimulatory role underscore relevant as mediators this process, uncover variety signaling pathways operates (Blood. 2003;102:662-671)