Expression and function of the angiopoietin receptor Tie-2 in human eosinophils.

Abstract

Increased vascularity of bronchial mucosa is closely related to the expression of angiogenic factors, which contribute to the pathogenesis of diseases such as asthma bronchiale. Here we examine the effects of the angiogenic growth factors angiopoietin 1 and angiopoietin 2 on eosinophil function in vitro and possible involvement of the angiopoietin receptor Tie-2. Eosinophil migration was studied by micropore filter assays. Signaling mechanisms required for angiopoietin-dependent migration were tested by using signaling enzyme blockers. Tie-2 mRNA and receptor expression on the cell surface of eosinophils was demonstrated in RT-PCR and by fluorescence-activated cell sorting analysis. Angiopoietin 1 significantly stimulated eosinophil chemotaxis via activation of phosphodiesterase, phosphatidylinositol 3'-kinase, and tyrosine kinases. The effect on eosinophil migration of angiopoietin 1 was reversed by an antibody against the Tie-2 receptor and by angiopoietin 2. Incubation of eosinophils with angiopoietin 1 abolished the chemotactic effects of vascular endothelial growth factor on human eosinophils via the Tie-2 receptor. Finally, Tie-2 expression by human eosinophils was demonstrated on the transcriptional and protein level. Data suggest that angiopoietin 1 stimulates directed migration and possibly inhibits vascular endothelial growth factor-induced eosinophil chemotaxis via its Tie-2 receptor, which is expressed by eosinophils. Thus, angiopoietin 1 may play an important role in the modulation of eosinophilic inflammation.