Glucocorticoid-induced surface expression of annexin 1 blocks beta2-integrin adhesion of human eosinophils to intercellular adhesion molecule 1 surrogate protein
التفاصيل البيبلوغرافية
العنوان:
Glucocorticoid-induced surface expression of annexin 1 blocks beta2-integrin adhesion of human eosinophils to intercellular adhesion molecule 1 surrogate protein
Background Glucocorticoids attenuate the population of eosinophils and T lymphocytes in asthmatic airways. The decrease in airway eosinophilia is caused both by accelerated cell death and by induction of blockade of integrin adhesion. In this study, we examined the hypothesis that annexin 1 surface expression, which is upregulated by the glucocorticoid receptor, prevents integrin adhesion essential to cell migration by blocking intracellular translocation of cytosolic group IV phospholipase A 2 (cPLA 2 ). Objective To examine the relationship of the glucocorticoid on annexin 1 expression and the effect of blockade of annexin 1 activity on adhesion of human eosinophils in vitro . To determine the relationship between annexin 1surface expression and nuclear membrane translocation of cPLA 2 . Methods Eosinophils isolated from human peripheral blood were pretreated with fluticasone propionate (FP), and β 2 -integrin adhesion was measured after stimulation with IL-5 or eotaxin. Effects of FP on cPLA 2 expression, phosphorylation, and translocation were determined. The role of annexin 1 was examined by using annexin 1 blocking antibody and/or mimetic peptides. Results Fluticasone propionate decreased stimulated eosinophil adhesion and caused 4-fold increase in annexin 1 expression on the plasma membrane. Inhibition of adhesion by FP was blocked with annexin 1 blocking antibody. Annexin 1 N-terminal mimetic peptide also blocked β 2 -integrin adhesion. Translocation of cPLA 2 to the nuclear membrane was significantly blocked by incubation with FP. Blockade was reversed with annexin 1 blocking antibody. Conclusion Blockade of β 2 -integrin adhesion by glucocorticoid is regulated by annexin 1, which blocks cPLA 2 translocation to nuclear membrane.
