CCR3-active chemokines influence eosinophil adhesion to endothelial cells under static and flow conditions

H. Tachimoto, M. Ebisawa, B. S. Bochner

Research output: Contribution to journalArticle

Abstract

We recently demonstrated that CCR3-active chemokines promote rapid detachment of eosinophils bound to vascular cell adhesion molecule-1 (VCAM-1) in vitro. Eosinophils adhered well to immobilized human recombinant VCAM-1 primarily via α4β1 integrin. Eotaxin-2, a CCR3-specific chemokine, induced eosinophil de-adhesion from VCAM-1. In contrast, very few eosinophils spontaneously adhered to bovine serum albumin (BSA), and eosinophil adhesion to BSA was enhanced by eotaxin-2 over a similar nm range of concentrations. This enhancement of BSA adhesion was dependent on β2 integrins. Eosinophil α4β1 integrins can mediate rolling on VCAM-1 under physiological flow conditions. Although we observed a reduction of eosinophil accumulation on immobilized VCAM-1 in response to eotaxin-2 under physiological flow conditions, this reduction of adhesion was not observed when VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) were co-immobilized. Based on antibody-blocking studies, this appears to be caused by a chemokine-induced shift in integrin usage away from β1 integrin-dominated interactions with VCAM-1 towards β2 integrin-dominated interactions with ICAM-1. Our results confirm the important role of integrins and chemokines in selective eosinophil migration processes. CCR3-active chemokines may be necessary to facilitate de-adhesion from luminal VCAM-1 and to facilitate the process of diapedesis by shifting integrin usage in eosinophils away from β1 integrin-dominated interactions with VCAM-1 towards β2 integrin-dominated interactions with ICAM-1. The critical importance of integrins and chemokines in eosinophilic inflammation lends support for targeting these molecules with novel therapeutic agents.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalClinical and Experimental Allergy Reviews
Volume7
Issue number1
DOIs
StatePublished - Aug 1 2007

Keywords

  • Adhesion molecules
  • Cell trafficking
  • Chemokines
  • Eosinophils
  • Human

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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