Angiopoietin Affects Neutrophil Migration

Abstract

Objective: After an ischemic event vascular growth factors are involved in regulating leukocyte infiltration in inflammatory processes. This study focused on effects of 2 other angiogenic growth factors, angiopoietin‐1 and angiopoietin‐2, on human neutrophils and on the involvement of the angiopoietin receptor Tie‐2. Methods: Neutrophils were from venous blood of healthy donors and cell migration was studied by micropore filter assays. Receptor expression was investigated by reverse transcriptase–polymerase chain reaction (PCR) for mRNA and fluorescence‐activated cell‐sorter scanner (FACS) analysis. Signaling mechanisms required for angiopoietin‐dependent effects were tested functionally by using signaling enzyme blockers. Results: The angiopoietins were chemotactic for neutrophils. They showed antagonistic effects on each other and both inhibited VEGF‐directed migration of neutrophils. The effects of both angiopoietins were Tie‐2 dependent. Tie‐2 receptor immunoreactivity was confirmed on neutrophils by FACS. De novo synthesis is suggested by Tie‐2 receptor mRNA expression as demonstrated by reverse transcriptase PCR. Conclusions: Data suggest that a Tie‐2 receptor is expressed by human neutrophils whose active site ligation with either angiopoietin‐1 or angiopoietin‐2 exerts migratory effects on the one hand and arrests VEGF‐mediated chemotaxis on the other. These effects suggest a role of angiopoietins in modulating neutrophilic inflammation.