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 language||English (US)|
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - 1995|
ASJC Scopus subject areas
- Immunology and Allergy