Angiopoietins can directly activate endothelial cells and neutrophils to promote proinflammatory responses.
Angiopoietin-1 (Ang1) and -2 (Ang2) are endothelial growth factors that bind to the tyrosine kinase receptor Tie2 and contribute to orchestrate blood vessel formation during angiogenesis. Ang1 mediates vessel maturation and integrity by the recruitment of pericytes. In contrast, Ang2 is classically considered as a Tie2 antagonist, counteracting the stabilizing action of Ang1. Inflammation exists in a mutually dependent association with angiogenesis and we have therefore studied the capacity of angiopoietins to modulate proinflammatory activities, namely P-selectin translocation and neutrophil adhesion onto endothelial cells. We observed that both Ang1 and Ang2 increased these biologic activities. Furthermore, combination of Ang1/Ang2 induced an additive effect on neutrophil adhesion but not on P-selectin translocation. In an attempt to clarify this phenomenon, we found that angiopoietins can directly activate neutrophils through Tie2 signaling as well as modulate platelet-activating factor (PAF) synthesis and beta(2) integrin functional up-regulation. Together, our data demonstrate that angiopoietins could promote acute recruitment of leukocytes, which might contribute to facilitate vascular remodeling and angiogenesis.
Lemieux
Caroline
C
Research Center, Montreal Heart Institute, Montreal, QC, Canada H1T 1C8.
Maliba
Ricardo
R
Favier
Judith
J
Théorêt
Jean-François
JF
Merhi
Yahye
Y
Sirois
Martin G
MG
D042683:Angiopoietin-1 / Q000502:physiology*; D042702:Angiopoietin-2 / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D018375:Neutrophil Activation / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology*; D019007:P-Selectin / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D042787:Receptor, TIE-2 / Q000096:biosynthesis / Q000378:metabolism; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018821:CD18 Antigens; D019007:P-Selectin; D010972:Platelet Activating Factor; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2