β2-Integrin adhesion caused by eotaxin but not IL-5 is blocked by PDE-4 inhibition and β2-adrenoceptor activation in human eosinophils

We investigated the effect and mechanism(s) of PDE-4 treatment with concurrent beta(2)-adrenoceptor stimulation on human eosinophil adhesion mediated by beta(2)-integrin in vitro. Eosinophils were pretreated with either rolipram, a PDE-4 inhibitor, alone or combined with salmeterol, a beta(2)-adrenoceptor agonist, before activation with either eotaxin or IL-5. beta(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 similar to 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, 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 beta(2)-integrin. IL5-induced adhesion likely utilizes a different upstream mechanism in regulation of integrin adhesion. (C) 2004 Elsevier Ltd. All rights reserved.