Intercellular Adhesion Molecule-1 Is Upregulated in Ischemic Muscle, Which Mediates Trafficking of Endothelial Progenitor Cells

Abstract

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. Methods and 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/␤-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.

Synergistic effect of HIF-1α gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia

“…Despite the lack of effect of DMOG-treated cells alone, the combination of IV DMOGtreated BMDACs and IM AdCA5 induced functional recovery and limb salvage in old mice, in which angiogenic responses are impaired as compared to young mice (4, 16), thus more closely resembling patients with critical limb ischemia. Finally, in addition to the synergistic therapeutic effects of IM AdCA5 and IV DMOG-treated BMDACs, stable retention of BMDACs in ischemic tissue is further aided by hypoxia-induced expression in vascular endothelial cells of ICAM-1 and E-selectin, which are known to interact with ␤ 2 integrins, and were recently shown to be involved in BMDAC homing to ischemic myocardium (35) and muscle (36,37).…”

The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium

“…Recently it was demonstrated that recruitment of CD34ϩ hematopoietic stem cells, the parent population of CD133ϩ EPCs, into the neovasculature of tumors utilizes the VCAM-1/ VLA-4 adhesive system (38). EPCs are recruited to ischemia-damaged muscle to reconstitute a functional microcirculation (32), and ICAM-1 plays a primary role in EPC recruitment to muscle (39). Ours is the first study to define the specific participation of the VCAM-1/ VLA-4 system, but not the ICAM/␤2 integrin subunit pair, in mediating EPC interactions with synovial cells.…”

Hypoxic regulation of neutrophil function and consequences for Staphylococcus aureus infection

“…[47]) with only one report (where reoxygenation was permitted after neutrophil isolation) finding no difference [44]. Although reports of modulation of ICAM-1 expression by hypoxia are conflicting [48,49], several studies have shown increased neutrophil adhesion to the endothelium under hypoxia (e.g. Ref.…”