EOTAXIN STIMULATES EOSINOPHIL ADHESION TO HUMAN LUNG MICROVASCULAR ENDOTHELIAL-CELLS

Effects of the human C-C chemokines eotaxin, MIP-1 alpha, and RANTES o n human eosinophil or neutrophil adhesion to human lung microvascular endothelial cells (LMVEC) were investigated. Basal adhesion of unstimu lated eosinophils to LMVEC was increased following pretreatment of LMV EC with TNF alpha (10ng/ml) for 6h. Stimulation of eosinophils with eo taxin (30 and 100ng/ml) resulted in increased adhesion to LMVEC pretre ated with TNF alpha but not culture medium, Neutrophil adhesion was no t increased by eotaxin under similar conditions. Neither MIP-1 alpha ( 3-100 ng/ml) nor RANTES (3-100ng/ml) increased eosinophil or neutrophi l adhesion to LMVEC pretreated for 6h with either TNF alpha (10ng/ml) or culture medium. Monoclonal antibodies (mAb) against eosinophil adhe sion molecule VLA-4 (2B4; 30 mu g/ml) but not CD18 (6.5E; 10 mu g/ml) inhibited eotaxin-induced eosinophil adhesion to TNF alpha-activated L MVEC. 2B4 in combination with 6.5E reduced adhesion to basal levels. T hese data show that eotaxin, but not MIP-1 alpha or RANTES, stimulates eosinophil adhesion to LMVEC and that this effect can be abolished by anti-VLA-4 and CD18 mAb in combination. These results suggest that eo taxin may facilitate eosinophil migration from blood vessels in the lu ng by increasing eosinophil adhesion to endothelial cells. (C) 1996 Ac ademic Press, Inc.