L-SELECTIN cross-linking signals cd 18integrin-dependent firm adhesion under conditions of flow

P. K. Gopalan, C. W. Smith, H. Lu, E. Berg, L. V. Mclntirer, S. I. Simon

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Neutrophil emigration across endothelial cells (EC) occurs in a sequential manner under shear conditions: rolling, firm adhesion, and transmigration. Rolling is mediated by selectins, while Firm adhesion and transmigration both require CD18 integrins. Activation is a prerequisite for CD 18 integrin function. However, the mechanisms by which CD18 integrins become activated upon contact with stimulated EC are not yet known. We have recently reported that cross-linking of L-selectin results in the rapid activation of CD18 integrin-dependent adhesion. We propose that under shear conditions, L-se!ectin ligation can signal CD 18 integrin activation that enables rolling neutrophils to adhere to endothelial surface receptors such asICAM-1 (CD54). Human CD54 and E-selectin (CD62E) were cotransfected into L cells where surface expression was comparable to that of cytokine-activated EC. Monolayers were placed in parallel plate flow chambers, and human neutrophil adhesion was evaluated at a wall shear stress of 2.0 dyn/cirf. Under these conditions, CD62E supported primary adhesion, and 23% of the roiling neutrophils stopped. The mean time from primary adhesion to stopping was 49 ±7 sec. Anti-CD54 monoclonal antibodies reduced stopping by 55%. When neutrophil L-selectin was cross-linked using a human chimera of DREG200 (that does not interact with FcRs on neutrophils) and goat anti-human F(ab% 49% of rolling neutrophils stopped within a mean of 15 ±5 sec. (pO.Ol). Anti-CD18 reduced this firm adhesion by 90%. These data support the conclusion that L-se!ectin can signal CD 18-dependent stationary adhesion of rolling neutrophils.

Original languageEnglish (US)
JournalFASEB Journal
Issue number6
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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