Signaling functions of L-selectin in neutrophils: Alterations in the cytoskeleton and colocalization with CD18

Scott I. Simon, Vera Cherapanov, Imad Nadra, Tom K. Waddell, Scott M. Seo, Qin Wang, Claire M. Doerschuk, Gregory P. Downey

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Ligation and clustering of L-selectin by Ab ('cross-linking') or physiologic ligands results in activation of diverse responses that favor enhanced microvascular sequestration and emigration of neutrophils. The earliest responses include a rise in intracellular calcium, enhanced tyrosine phosphorylation, and activation of extracellular signal-regulated kinases. Additionally, cross-linking of L-selectin induces sustained shape change and activation of β2 integrins, leading to neutrophil arrest under conditions of shear flow. In this report, we examined several possible mechanisms whereby transmembrane signals from L-selectin might contribute to an increase in the microvascular retention of neutrophils and enhanced efficiency of emigration. In human peripheral blood neutrophils, cross-linking of L- selectin induced alterations in cellular biophysical properties, including a decrease in cell deformability associated with F-actin assembly and redistribution, as well as enhanced adhesion of microspheres bound to β2 integrins. L-selectin and the β2 integrin became spatially colocalized as determined by confocal immunofluorescence microscopy and fluorescence resonance energy transfer. We conclude that intracellular signals from L- selectin may enhance the microvascular sequestration of neutrophils at sites of inflammation through a combination of cytoskeletal alterations leading to cell stiffening and an increase in adhesiveness mediated through alterations in β2 integrins.

Original languageEnglish (US)
Pages (from-to)2891-2901
Number of pages11
JournalJournal of Immunology
Volume163
Issue number5
StatePublished - Sep 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Simon, S. I., Cherapanov, V., Nadra, I., Waddell, T. K., Seo, S. M., Wang, Q., Doerschuk, C. M., & Downey, G. P. (1999). Signaling functions of L-selectin in neutrophils: Alterations in the cytoskeleton and colocalization with CD18. Journal of Immunology, 163(5), 2891-2901.