β 2-Integrin adhesion caused by eotaxin but not IL-5 is blocked by PDE-4 inhibition and β 2-adrenoceptor activation in human eosinophils

Abstract

We investigated the effect and mechanism(s) of PDE-4 treatment with concurrent β 2-adrenoceptor stimulation on human eosinophil adhesion mediated by β 2-integrin in vitro. Eosinophils were pretreated with either rolipram, a PDE-4 inhibitor, alone or combined with salmeterol, a β 2-adrenoceptor agonist, before activation with either eotaxin or IL-5. β 2-integrin mediated adhesion was assessed as adherence to BSA, an established surrogate for ICAM-1. Rolipram caused progressive blockade (77.7±6.2%) of adhesion elicited by eotaxin. Maximal blockade of IL-5-activated adhesion by rolipram was substantially less (29.9±5.2%). Salmeterol+rolipram synergistically enhanced the blockade of eotaxin-activated adhesion. Eotaxin also caused ∼50% increase in surface CD11b expression, which was blocked additively by rolipram+salmeterol. By contrast, CD11b upregulation caused by IL-5 was not blocked by rolipram+salmeterol. Rolipram also attenuated cPLA 2 phosphorylation caused by eotaxin but did not block IL-5-induced phosphorylation. We conclude that rolipram blocks expression of CD11b and inhibits cPLA 2 phosphorylation in human eosinophils, thus blocking eotaxin-induced adhesion of β 2-integrin. IL-5-induced adhesion likely utilizes a different upstream mechanism in regulation of integrin adhesion.