Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions

We have recently cloned eotaxin, a highly efficacious eosinophilic chemokin e involved in the development of lung eosinophilia during allergic inflamma tory reactions. To understand more precisely how eotaxin facilitates the sp ecific migration of eosinophils, we have studied which adhesion receptors a re essential for eotaxin action both in vivo and in vitro. Experiments usin g mice genetically deficient in adhesion receptors demonstrated that molecu les previously reported to be involved in both leukocyte tethering/rolling (P-selectin and E-selectin) and in sticking/transmigration (ICAM-1 and VCAM -1) are required for eotaxin action in vivo, To further elucidate the mecha nism(s) involved in this process, we have used an in vitro transendothelial chemotaxis model. mAb neutralization studies performed in this system sugg est that the integrins Mac-1 (CD11b/18), VLA-4 (alpha(4)beta(1)) and LFA-1 (CD11a/18) are involved in the transendothelial chemotaxis of eosinophils t o eotaxin, Accordingly, the expression of these integrins on eosinophils is elevated by direct action of this chemokine in a concentration-dependent m anner. Taken together, our results suggest that eotaxin-induced eosinophil transendothelial migration in vivo and in vitro relies on Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions, the latter ones becoming more relevant at later time points of the eotaxin-induced recruitment process.