Neutrophil CD18-Dependent Arrest on Intercellular Adhesion Molecule 1 (ICAM-1) in Shear Flow Can Be Activated Through L-Selectin

Priya K. Gopalan, C. Wayne Smith, Huifang Lu, Ellen L. Berg, Larry V. McIntire, Scott I. Simon

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Neutrophil emigration through endothelial cells under shear flow involves several adhesion processes including cell rolling, arrest, and transmigration. Rolling is mediated by selectins, while arrest and transmigration both require activated CD18 integrins. One mode of CD18 activation is via selectins expressed on neutrophils and endothelial cells. We have recently reported that cross-linking of L-selectin (CD62L) resulted in the rapid activation of CD18-dependent adhesion. In the current study, we examine whether binding of E-selectin (CD62E) and L-selectin can activate neutrophil CD18-dependent adhesion under shear flow. Human ICAM-1 (CD54) and E-selectin were co-transfected into L cells. Neutrophil capture, rolling, and arrest on these monolayers were quantitated in a parallel plate flow chamber at a wall shear stress of 2.0 dyne/cm2. Under these conditions, E-selectin supported cell capture and rolling on the monolayer, but did not trigger CD18-mediated cell arrest within 200 μm of rolling. However, when neutrophils were treated with anti-L-selectin mAb and cross-linked with a secondary mAb, approximately 50% of the cells arrested within 54 μm. Cell arrest was also observed in response to IL-8 stimulation. A subthreshold level of IL-8 in combination with L-selectin cross-linking potentiated the level of cell arrest due to either stimulus alone. The transition to cell arrest involved both LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Blocking either subunit alone failed to reduce arrest, while blocking both molecules with mAbs reduced the number to baseline levels. These data support the conclusion that L-selectin, but not E-selectin, can signal the transition from neutrophil rolling to cell arrest under shear flow.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
JournalJournal of Immunology
Volume158
Issue number1
StatePublished - Jan 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Gopalan, P. K., Smith, C. W., Lu, H., Berg, E. L., McIntire, L. V., & Simon, S. I. (1997). Neutrophil CD18-Dependent Arrest on Intercellular Adhesion Molecule 1 (ICAM-1) in Shear Flow Can Be Activated Through L-Selectin. Journal of Immunology, 158(1), 367-375.