EFFECTS OF TGF-BETA ON EOSINOPHIL CHEMOTAXIS

Transforming growth factor-beta (TGF-beta), which can decrease the eff ects of interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-sti mulating factor (GM-CSF) on eosinophil viability, has been shown to be chemotactic for neutrophils. However, there is little information on its effects on eosinophil chemotaxis. Because TGF-beta has recently be en found in increased concentrations in asthmatic sputum, we investiga ted whether TGF-beta could influence eosinophil migration and eosinoph il viability. Purified eosinophils from normal donors were incubated w ith increasing concentrations of TGF-beta. Chemotaxis was measured wit h a modified Boyden chamber technique. In addition, eosinophils were i ncubated for 96 h with either IL-3, IL-5 or GM-CSF (1 ng/ml) together with increasing concentrations of TGF-beta. Eosinophil viability was t hen determined with propidium jodide and flowcytometry. Eosinophil che motaxis was significantly increased in the presence of TGF-beta in con centrations between 10(-9) and 10(-4) mu g/ml. The optimal concentrati on of TGF-beta in this assay was between 10(-9) and 10(-8) mu g/ml. Th e chemotactic effect of TGF-beta diminished when higher as well as low er concentrations (between 10(-12) and 10(-3) mu g/ml) were employed. In contrast, inhibition of eosinophil survival induced by IL-3, IL-5 a nd GM-CSF reached its maximum at concentrations of TGF-beta between 10 (-4) and 10(-3) mu g/ml. From these data we conclude that TGF-beta in low concentrations can induce eosinophil chemotaxis whereas higher con centrations reduce eosinophil survival mediated by IL-3, IL-5 and GM-C SF.