Leukotriene D4 upregulates eosinophil adhesion via the cysteinyl leukotriene 1 receptor

Abstract

Background: Eosinophils (EOS) are one of the cellular sources of cysteinyl leukotrienes (cysLTs) in allergic inflammation. There is evidence that cysLT1 receptor antagonists possess anti-inflammatory properties in vivo in asthmatic airways. Although the exact mechanism of action remains unknown, cysLTs might regulate the cellular responses involved in allergic inflammation. Objective: The present study was undertaken to examine whether LTD4 modifies the adhesive property of EOS. Methods: EOS were isolated from the blood of healthy subjects. Their adhesion to tissue culture plates or recombinant human (rh) adhesion proteins was then examined in the presence or absence of LTD4. Results: LTD4 significantly augmented EOS adhesion to tissue culture plates (adhesion: 5.0% ± 0.5% by medium control vs 9.1% ± 1.2% by 1 μmol/L; P < .01; n = 10). The enhanced adhesion induced by LTD4 was blocked by pranlukast, a cysLT1 receptor antagonist, or an anti-β2 integrin antibody. Flow cytometry analysis revealed that LTD4 significantly enhanced the expression of CD11b and CD18 on the EOS surface. Finally, LTD4 augmented EOS adhesion to rh intercellular cell adhesion molecule 1 but not to rh vascular cell adhesion molecule 1 or fibronectin. Conclusions: The results suggest that LTD4 directly upregulates the adhesive property of EOS via the cysLT1 receptor and β2 integrin. LTD4 generated from EOS or cells of some other type might contribute to the development of phenotypic change in airway EOS.