Ionomycin causes activation of p38 and p42/44 mitogen-activated protein kinases in human neutrophils.
Ionomycin causes activation of p38 and p42/44 mitogen-activated protein kinases in human neutrophils.
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DOI：
10.1152/ajpcell.2001.281.1.c350
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发表时间：
2001-07
期刊：
影响因子：
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通讯作者：
David J. Elzi;A. J. Bjornsen;Todd MacKenzie;Travis H. Wyman;Christopher C. Silliman;Christopher C. Silliman
中科院分区：
文献类型：
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作者：
David J. Elzi;A. J. Bjornsen;Todd MacKenzie;Travis H. Wyman;Christopher C. Silliman;Christopher C. Silliman
Many receptor-linked agents that prime or activate the NADPH oxidase in polymorphonuclear neutrophils (PMNs) elicit changes in cytosolic Ca2+ concentration and activate mitogen-activated protein (MAP) kinases. To investigate the role of Ca2+ in the activation of p38 and p42/44 MAP kinases, we examined the effects of the Ca2+-selective ionophore ionomycin on priming and activation of the PMN oxidase. Ionomycin caused a rapid rise in cytosolic Ca2+ that was due to both a release of cytosolic Ca2+ stores and Ca2+ influx. Ionomycin also activated (2 microM) and primed (20-200 nM) the PMN oxidase. Dual phosphorylation of p38 MAP kinase and phosphorylation of its substrate activating transcription factor-2 were detected at ionomycin concentrations that prime or activate the PMN oxidase, while dual phosphorylation of p42/44 MAP kinase and phosphorylation of its substrate Elk-1 were elicited at 0.2-2 microM. SB-203580, a p38 MAP kinase antagonist, inhibited ionomycin-induced activation of the oxidase (68 +/- 8%, P < 0.05) and tyrosine phosphorylation of 105- and 72-kDa proteins; conversely, PD-98059, an inhibitor of MAP/extracellular signal-related kinase 1, had no effect. Treatment of PMNs with thapsigargin resulted in priming of the oxidase and activation of p38 MAP kinase. Chelation of cytosolic but not extracellular Ca2+ completely inhibited ionomycin activation of p38 MAP kinase, whereas chelation of extracellular Ca2+ abrogated activation of p42/44 MAP kinase. These results demonstrate the importance of changes in cytosolic Ca2+ for MAP kinase activation in PMNs.
