Eosinophil adhesion to vascular cell adhesion molecule-1 activates superoxide anion generation

M. Nagata, J. B. Sedgwick, M. E. Bates, H. Kita, W. W. Busse

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108 Scopus citations

Abstract

Adhesion to the adhesion protein, VCAM-1, on vascular endothelium is proposed to be an important factor in the selective accumulation of eosinophils at sites of allergic inflammation. To determine whether eosinophil adhesion to VCAM-1 is also associated with an alteration of eosinophil function, human peripheral blood eosinophils were isolated from allergic donors and incubated in VCAM-1 -coated wells. Spontaneous adherence of isolated eosinophils to VCAM-1 -coated wells was greater than cells incubated in FCS-treated control wells (38.0 ± 1.6% vs 17.1 ± 1.9%, n = 16, p < 0.0001). In addition, eosinophils incubated in VCAM-1-coated wells spontaneously generated modest but significant amounts of superoxide anion (O2-; 2.0 ± 1.3 vs 0.5 ± 0.5 nmol/5 x 105 cells, n = 9, p = 0.029). Moreover, when 100 nM FMLP was added to eosinophils in the presence of VCAM- 1, significantly greater O2- generation occurred (7.2 ± 0.9 vs 5.4 ± 1.0 (FCS control) nmol/5 x 105 cells, n = 9, p = 0.009). Adhesion, as well as the spontaneous and enhanced O2- generation to FMLP activation, was blocked by the monoclonal anti-α4 integrin Ab, HP 1/2 , implying involvement of an α4 integrin-VCAM-1 interaction. In contrast, the anti-CD18 mAb, L130, inhibited the spontaneous and enhanced O2- generation to FMLP without affecting adhesion, suggesting an involvement of CD18 molecule(s) only in VCAM-1-enhanced respiratory burst. Finally, 1 μM genistein, a tyrosine kinase inhibitor, suppressed the VCAM-1-enhancing effect on eosinophil O2- generation and VCAM-1-induced tyrosine phosphorylation, suggesting a role for tyrosine phosphorylation in this eosinophil functional up-regulation. Our observations suggest that eosinophil adhesion to VCAM-1 may be an important step in determining the eventual functional activity of these cells as they migrate from the circulation to the airways and contribute to the allergic inflammatory process.

Original languageEnglish (US)
Pages (from-to)2194-2202
Number of pages9
JournalJournal of Immunology
Volume155
Issue number4
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nagata, M., Sedgwick, J. B., Bates, M. E., Kita, H., & Busse, W. W. (1995). Eosinophil adhesion to vascular cell adhesion molecule-1 activates superoxide anion generation. Journal of Immunology, 155(4), 2194-2202.