Angiopoietin affects neutrophil migration.
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.
Sturn
Daniel H
DH
Division of General Internal Medicine, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Feistritzer
Clemens
C
Mosheimer
Birgit A
BA
Djanani
Angela
A
Bijuklic
Klaudija
K
Patsch
Josef R
JR
Wiedermann
Christian J
CJ
D042683:Angiopoietin-1 / Q000502:physiology*; D042702:Angiopoietin-2 / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D042787:Receptor, TIE-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2