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Ionomycin caused a rapid rise in cytosolic Ca<jats:sup>2+<\/jats:sup> that was due to both a release of cytosolic Ca<jats:sup>2+<\/jats:sup> stores and Ca<jats:sup>2+<\/jats:sup> influx. Ionomycin also activated (2 \u03bcM) and primed (20\u2013200 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\u20132 \u03bcM. SB-203580, a p38 MAP kinase antagonist, inhibited ionomycin-induced activation of the oxidase (68 \u00b1 8%, P &lt; 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 Ca<jats:sup>2+<\/jats:sup> completely inhibited ionomycin activation of p38 MAP kinase, whereas chelation of extracellular Ca<jats:sup>2+<\/jats:sup> abrogated activation of p42\/44 MAP kinase. These results demonstrate the importance of changes in cytosolic Ca<jats:sup>2+<\/jats:sup> for MAP kinase activation in PMNs. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.1.c350","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:05:28Z","timestamp":1514145928000},"page":"C350-C360","source":"Crossref","is-referenced-by-count":45,"title":["Ionomycin causes activation of p38 and p42\/44 mitogen-activated protein kinases in human neutrophils"],"prefix":"10.1152","volume":"281","author":[{"given":"David J.","family":"Elzi","sequence":"first","affiliation":[{"name":"Bonfils Blood Center, Denver 80230; and Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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