Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells.
BACKGROUND
Trafficking of transplanted endothelial progenitor cells (EPCs) to an ischemic organ is a critical step in neovascularization. This study was performed to elucidate the molecular mechanism of EPC trafficking in terms of adhesion molecules.


RESULTS
Using murine hindlimb ischemia model, we examined expressions of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in ischemic muscle by immunofluorescence. ICAM-1 was overexpressed in ischemic muscle compared with nonischemic muscle, whereas expressions of E-selectin, VCAM-1, and PECAM-1 did not show that much difference. ICAM-1 was also upregulated by hypoxia in murine endothelial cells (ECs) as assessed by immunoblot and flow cytometry. EPCs were attached to ECs specifically through ICAM-1/beta-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrated in vivo, EPCs preferentially homed to ischemic muscle. By blocking ICAM-1, EPCs entrapment to ischemic limb in vivo was significantly reduced and neovascularization induced by EPC transplantation was attenuated.


CONCLUSIONS
ICAM-1 is upregulated by ischemia, and this is closely associated with EPCs entrapment to ischemic limb. Our findings suggest that ICAM-1 expression might be important in regulating the process of neovascularization through its ability to recruit EPCs.
Yoon
Chang-Hwan
CH
Cardiovascular Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Hur
Jin
J
Oh
Il-Young
IY
Park
Kyung-Woo
KW
Kim
Tae-Youn
TY
Shin
Jae-Hoon
JH
Kim
Ji-Hyun
JH
Lee
Choon-Soo
CS
Chung
June-Key
JK
Park
Young-Bae
YB
Kim
Hyo-Soo
HS
D000818:Animals; D018821:CD18 Antigens / Q000235:genetics; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006614:Hindlimb / Q000098:blood supply; D007249:Inflammation / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D033581:Stem Cell Transplantation
D018821:CD18 Antigens; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1