L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase

James E. Smolen, Thomas K. Petersen, Cody Koch, Stephen J. O'Keefe, William A. Hanlon, Scott Seo, David Pearson, Milligan C. Fossett, Scott I. Simon

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124 Scopus citations

Abstract

The adhesion molecules known as selectins mediate the capture of neutrophils from the bloodstream. We have previously reported that ligation and cross-linking of L-selectin on the neutrophil surface enhances the adhesive function of β2-integrins in a synergistic manner with chemotactic agonists. In this work, we examined degranulation and adhesion of neutrophils in response to cross-linking of L-selectin and addition of interleukin-8. Cross-linking of L-selectin induced priming of degranulation that was similar to that observed with the alkaloid cytochalasin B. Activation mediated by L- selectin of neutrophil shape change and adhesion through CD11b/CD18 were strongly blocked by Merck C, an imidazole-based inhibitor of p38 mitogen- activated protein kinase (MAPK), but not by a structurally similar non- binding regioisomer. Priming by L-selectin of the release of secondary, tertiary, and secretory, but not primary, granules was blocked by inhibition of p38 MAPK. Peak phosphorylation of p38 MAPK was observed within 1 rain of cross-linking L-selectin, whereas phosphorylation of ERK1/2 was highest at 10 min. Phosphorylation of p38 MAPK, but not ERK1/2, was inhibited by Merck C. These data suggest that signal transduction as a result of clustering L- selectin utilizes p38 MAPK to effect neutrophil shape change, integrin activation, and the release of secondary, tertiary, and secretory granules.

Original languageEnglish (US)
Pages (from-to)15876-15884
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number21
DOIs
StatePublished - May 26 2000

ASJC Scopus subject areas

  • Biochemistry

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    Smolen, J. E., Petersen, T. K., Koch, C., O'Keefe, S. J., Hanlon, W. A., Seo, S., Pearson, D., Fossett, M. C., & Simon, S. I. (2000). L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase. Journal of Biological Chemistry, 275(21), 15876-15884. https://doi.org/10.1074/jbc.M906232199