Role of beta2-integrins for homing and neovascularization capacity of endothelial progenitor cells.
The mechanisms of homing of endothelial progenitor cells (EPCs) to sites of ischemia are unclear. Here, we demonstrate that ex vivo-expanded EPCs as well as murine hematopoietic Sca-1+/Lin- progenitor cells express beta2-integrins, which mediate the adhesion of EPCs to endothelial cell monolayers and their chemokine-induced transendothelial migration in vitro. In a murine model of hind limb ischemia, Sca-1+/Lin- hematopoietic progenitor cells from beta2-integrin-deficient mice are less capable of homing to sites of ischemia and of improving neovascularization. Preactivation of the beta2-integrins expressed on EPCs by activating antibodies augments the EPC-induced neovascularization in vivo. These results provide evidence for a novel function of beta2-integrins in postnatal vasculogenesis.
Chavakis
Emmanouil
E
Molecular Cardiology, Dept. of Medicine III, University of Frankfurt, 60950 Frankfurt, Germany.
Aicher
Alexandra
A
Heeschen
Christopher
C
Sasaki
Ken-ichiro
K
Kaiser
Ralf
R
El Makhfi
Naual
N
Urbich
Carmen
C
Peters
Thorsten
T
Scharffetter-Kochanek
Karin
K
Zeiher
Andreas M
AM
Chavakis
Triantafyllos
T
Dimmeler
Stefanie
S
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
D018821:CD18 Antigens