Regulation of α4 integrin-mediated adhesion of human eosinophils to fibronectin and vascular cell adhesion molecule-1

Kenji Matsumoto, Sherry A. Sterbinsky, Carol A. Bickel, David F H Zhou, Nicholas L. Kovach, Bruce S. Bochner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Eosinophils selectively accumulate at sites of allergic inflammation. Their recruitment is dependent on both the expression and functional activity of cell adhesion molecules. How the functional activity of cell adhesion molecules on eosinophils is regulated is poorly understood. Objective: Our objective was to examine the functional activity of α4 integrins on human eosinophils and its regulation by various agents. Methods: Function of α4 integrins on human eosinophils was examined by testing adhesion to immobilized fibronectin and vascular cell adhesion molecule-1 (VCAM-1) in the presence or absence of a monoclonal antibody (mAb) (8A2) that activates β1 integrin functions. Results: Spontaneous eosinophil adhesion to VCAM-1 was enhanced by 8A2, but adhesion to fibronectin could only be detected in the presence of 8A2. Concentrations of 8A2 that were approximately 100-fold less than saturating induced maximal eosinophil adhesion. Adhesion to VCAM-1 in the presence of 8A2 was effectively inhibited by α4 and β1 integrin mAbs; β7 mAb had partial inhibitory activity. Connecting segment-1 peptide and α4 mAb blocked 8A2-dependent fibronectin binding; β1, β2, and β7 integrin mAbs had partial inhibitory activity. Eosinophils obtained from bronchoalveolar lavage fluids and blood eosinophils stimulated with IL-5, platelet-activating factor, or RANTES displayed increased β2 integrin- dependent, not α4 integrin-dependent, attachment. Spontaneous adhesion of eosinophils to VCAM-1 was significantly reduced by the tyrosine kinase inhibitor tyrphostin B46 (inhibitory concentration of 50% α 20 μmol/L); this effect was reversed by 8A2. Conclusions: The functional activity of integrins on eosinophils can be positively and negatively regulated. Altered integrin avidity may influence eosinophil recruitment in vivo.

Original languageEnglish (US)
Pages (from-to)648-656
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume99
Issue number5
DOIs
StatePublished - 1997

Keywords

  • Eosinophil
  • adhesion
  • fibronectin
  • integrin
  • integrin function
  • vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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