EOSINOPHIL TRANSENDOTHELIAL MIGRATION INDUCED BY CYTOKINES .2. POTENTIATION OF EOSINOPHIL TRANSENDOTHELIAL MIGRATION BY EOSINOPHIL-ACTIVE CYTOKINES

Activation of HUVEC monolayers by IL-1 beta or TNF-alpha induces migra tion of eosinophils across the endothelial monolayer (i.e., transendot helial migration) in vitro. In the present study, we demonstrate that culture of freshly isolated eosinophils in the presence of IL-5 for 24 to 48 h before use in the assay dramatically potentiated CD18-depende nt eosinophil transendothelial migration through unstimulated endothel ial monolayers. Granulecyte macrophage (GM)-CSF induced eosinophil tra nsendothelial migration but did not induce neutrophil transendothelial migration. When IL-1 beta-activated endothelial cells were used, GM-C SF, IL-3, or IL-5 caused only modest potentiation of eosinophil transe ndothelial migration. Since activated endothelial cells are known to p roduce GM-CSF, we hypothesized that endothelial-derived CM-CSF might p lay a role in the process of IL-1 beta-induced eosinophil transendothe lial migration. IL-1 beta-activated endothelial monolayers grown on th e permeable supports produced 0.3 +/- 0.1 ng/ml of GM-CSF during a 4-h incubation and neutralizing Ab against GM-CSF inhibited eosinophil tr ansendothelial migration by 48%, suggesting that endothelial-derived G M-CSF may participate in the response. Eosinophils purified from bronc hoalveolar lavage 18 to 20 h after experimental Ag challenge in the lu ngs of allergic volunteers showed enhanced transendothelial migration, indicating that the cells may have undergone cytokine activation in v ivo. Eosinophil-active cytokines may contribute to the preferential ac cumulation of eosinophils in vivo in part via potentiation of eosinoph il transendothelial migration.