Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration

Yvonne T M Tsang, Sriram Neelamegham, Yu Hu, Ellen L. Berg, Alan R. Burns, C. Wayne Smith, Scott I. Simon

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

L-selectin enables capture and rolling of neutrophils on inflamed endothelium. This may facilitate the binding of agonists such as IL-8 and platelet-activating factor (PAF), which signal CD18-mediated firm adhesion and transmigration. Recent studies demonstrate that L-selectin can mediate transmembrane signaling. However, the functional effects of costimulation through agonist and L-selectin require further study. Here, we quantify cell adhesion, motility, and transmigration in response to co-activation through L-selectin and agonist. The surface expression of CD11b/CD18 increased and L-selectin decreased in proportion to the extent of L-selectin cross-linking. A flow cytometric assay was used to measure CD11b/CD18-dependent adhesion to fluorescent beads adsorbed with albumin. Neutrophil adhesion was detected within seconds of adding PAF (20 pM), IL-8 (50 pM), or cross-linking L-selectin. Costimulation through agonist and L-selectin potentiated by up to threefold the rate and extent of bead capture. Stimulation through L-selectin induced membrane ruffling, whereas PAF or IL-8 induced bipolar shape change. L-selectin cross-linking sustained the transient shape change induced by low concentrations (10-50 pM) of agonist. Chemokinesis stimulated by IL-8 was inhibited in the presence of cross-linking L-selectin. This was attributed to enhanced cell spreading following costimulation. Migration across HUVEC monolayers stimulated with IL-1 was also potentiated in the presence of L-selectin cross-linking. We propose that cross-linking of L-selectin and binding of agonist receptors may act synergistically to amplify neutrophil activation and emigration in the inflamed vasculature.

Original languageEnglish (US)
Pages (from-to)4566-4577
Number of pages12
JournalJournal of Immunology
Volume159
Issue number9
StatePublished - Nov 1 1997
Externally publishedYes

Fingerprint

L-Selectin
Neutrophil Activation
Interleukin-8
Platelet Activating Factor
Neutrophils
Emigration and Immigration
Interleukin-1
Cell Adhesion
Endothelium
Cell Movement
Albumins

ASJC Scopus subject areas

  • Immunology

Cite this

Tsang, Y. T. M., Neelamegham, S., Hu, Y., Berg, E. L., Burns, A. R., Smith, C. W., & Simon, S. I. (1997). Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration. Journal of Immunology, 159(9), 4566-4577.

Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration. / Tsang, Yvonne T M; Neelamegham, Sriram; Hu, Yu; Berg, Ellen L.; Burns, Alan R.; Smith, C. Wayne; Simon, Scott I.

In: Journal of Immunology, Vol. 159, No. 9, 01.11.1997, p. 4566-4577.

Research output: Contribution to journalArticle

Tsang, YTM, Neelamegham, S, Hu, Y, Berg, EL, Burns, AR, Smith, CW & Simon, SI 1997, 'Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration', Journal of Immunology, vol. 159, no. 9, pp. 4566-4577.
Tsang YTM, Neelamegham S, Hu Y, Berg EL, Burns AR, Smith CW et al. Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration. Journal of Immunology. 1997 Nov 1;159(9):4566-4577.
Tsang, Yvonne T M ; Neelamegham, Sriram ; Hu, Yu ; Berg, Ellen L. ; Burns, Alan R. ; Smith, C. Wayne ; Simon, Scott I. / Synergy between L-Selectin Signaling and Chemotactic Activation during Neutrophil Adhesion and Transmigration. In: Journal of Immunology. 1997 ; Vol. 159, No. 9. pp. 4566-4577.
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