Functional Regulation of β1 Integrins on Human Eosinophils by Divalent Cations and Cytokines

Sabine J. Werfel, Ted A. Yednock, Kenji Matsumoto, Sherry A. Sterbinsky, Robert P. Schleimer, Bruce S. Bochner

Research output: Contribution to journalArticle

Abstract

Divalent cations and various soluble stimuli can alter cell adherence by affecting the avidity of adhesion molecules. We hypothesized that β1 integrin function of human eosinophils may be altered by divalent cations and eosinophil-activating cytokines such as interleukin-5 (IL-5). Expression of the β1 integrin activation epitope recognized by monoclonal antibody (mAb) 15/7 was evaluated by flow cytometry using purified eosinophils from allergic subjects, normal subjects, and late-phase bronchoalveolar lavage (BAL) fluids. Rapid and reversible 15/7 binding on eosinophils from each source was induced in Mn2+ (0.01-1 mM) but not in buffers containing other divalent cations and occurred without affecting the total level of β1 integrin expression (quantified using mAb 33B6). Augmentation of eosinophil adhesion to immobilized vascular cell adhesion molecule (VCAM-1) in Mn2+ followed a similar concentration dependence as mAb 15/7 binding. Net binding to VCAM-1 in Mn2+ was completely inhibited with a mixture of α4 and β1 integrin mAb while β2 integrin mAb had no effect. Exposure of eosinophils from allergic subjects to as little as 1 pg/ml IL-5 completely inhibited mAb 15/7 binding induced by Mn2+. In contrast, increased binding of mAb 15/7 in Mn2+ was not blocked by IL-5 in eosinophils from normal subjects. For eosinophils from allergic subjects, IL-5 also inhibited Mn2+-induced adhesion to VCAM-1. Thus, β1 integrins on eosinophils from allergic and nonallergic subjects are modulated differently by Mn2+ and IL-5. Altered β1 integrin avidity may be one mechanism involved in preferential eosinophil recruitment in vivo.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume14
Issue number1
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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