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

Research output: Contribution to journalArticle

122 Citations (Scopus)

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

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L-Selectin
p38 Mitogen-Activated Protein Kinases
Neutrophils
Adhesion
Phosphorylation
Integrins
Chemical activation
Selectins
Signal transduction
Cytochalasin B
Rain
Secretory Vesicles
Interleukin-8
Alkaloids
Adhesives
Ligation
Cluster Analysis
Signal Transduction
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Smolen, J. E., Petersen, T. K., Koch, C., O'Keefe, S. J., Hanlon, W. A., Seo, S., ... 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

L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase. / Smolen, James E.; Petersen, Thomas K.; Koch, Cody; O'Keefe, Stephen J.; Hanlon, William A.; Seo, Scott; Pearson, David; Fossett, Milligan C.; Simon, Scott I.

In: Journal of Biological Chemistry, Vol. 275, No. 21, 26.05.2000, p. 15876-15884.

Research output: Contribution to journalArticle

Smolen, JE, Petersen, TK, Koch, C, O'Keefe, SJ, Hanlon, WA, Seo, S, Pearson, D, Fossett, MC & Simon, SI 2000, 'L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase', Journal of Biological Chemistry, vol. 275, no. 21, pp. 15876-15884. https://doi.org/10.1074/jbc.M906232199
Smolen, James E. ; Petersen, Thomas K. ; Koch, Cody ; O'Keefe, Stephen J. ; Hanlon, William A. ; Seo, Scott ; Pearson, David ; Fossett, Milligan C. ; Simon, Scott I. / L-selectin signaling of neutrophil adhesion and degranulation involves p38 mitogen-activated protein kinase. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 21. pp. 15876-15884.
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