VCAM-1 has a tissue-specific role in mediating interleukin-4-induced eosinophil accumulation in rat models: evidence for a dissociation between endothelial-cell VCAM-1 expression and a functional role in eosinophil migration

Eosinophil accumulation has been associated with the pathogenesis of numero us allergic inflammatory disorders. Despite the great interest in this resp onse, many aspects of eosinophil accumulation remain unknown. This is parti cularly true with respect to tissue-specific mechanisms that may regulate t he accumulation of eosinophils in different organs. This study addressed th is issue by investigating and comparing the roles of alpha (4)-integrins an d vascular cell adhesion molecule 1 (VCAM 1) adhesion pathways in interleuk in 4 (IL-4)-induced eosinophil accumulation in 2 different rat models of in flammation, namely pleural and cutaneous inflammation. Similar to our previ ous findings in studies in rat skin, locally administered IL-4 induced a ti me- and dose-dependent accumulation of eosinophils in rat pleural cavities, a response that was associated with generation of the chemokine eotaxin, T he IL-4-induced eosinophil accumulation in skin and pleural cavities was to tally inhibited by an antirat alpha (4)-integrins monoclonal antibody (mAb) (TA-2). In contrast, whereas an antirat VCAM-1 mAb (5F10)totally blocked t he response in skin, IL-4-induced eosinophil accumulation in rat pleural ca vities was not affected by VCAM-1 blockade. A radiolabeled mAb technique de monstrated that endothelial-cell VCAM-1 expression was induced in response to IL-4 in both skin and pleural membrane, The results indicate that althou gh endothelial-cell VCAM-1 is present in skin and pleura, a functional role for it in IL-4-induced eosinophil accumulation was evident only in skin. T hese findings suggest the existence of tissue-specific adhesive mechanisms in regulating leukocyte migration in vivo and demonstrate a dissociation be tween VCAM-1 expression and eosinophil accumulation. (C) 2000 by The Americ an Society of Hematology.