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ȣ - 480203 262 |
| E-selectin Augments Homing and Angiogenesis of Endothelial Progenitor Cell |
| 서울대학교의과대학 내과학교실¹ ; 서울대학교병원 임상의학연구소 심혈관연구실² ; 서울대학교병원 심혈관센터³ |
| 오일영¹ ² ³, 김지현² , 허진² , 윤창환² , 전수인² , 김태연² , 손대원¹ ² ³, 오병희¹ ² ³ , 이명묵¹ ² ³, 박영배¹ ² ³ , 최윤식¹ ² ³, 김효수¹ ² ³ |
Background: E-selectin is an endothelial specific lectin that plays a critical role in tethering of leukocytes or hematopoietic progenitors to endothelial cells. Soluble E-selectin, which is shedded from membrane-bound E-selectin, is a potent angiogenic mediator. Here we assessed the hypothesis that membrane-bound E-selectin plays an important role in endothelial progenitor cell (EPC) homing and that soluble E-selectin augments angiogenesis of EPC.
Methods and Results: We showed that human EPCs expressed both E-selectin ligand and fucosyltransferase-VII. In vitro modified Boyden chamber assay showed a dose-dependent EPC migration toward recombinant human soluble E-selectin (rh-E-selectin) (control vs. 0.5 μg/ml vs. 5 μg/ml = 31 ± 4 vs. 40 ± 4 vs. 58 ± 10 cells/mm2, P < 0.01). Furthermore, rh-E-selectin induced a 1.8 fold increase in capillary tube formation on matrigel (control versus rh-E-selectin = 0.40 vs. 0.72 mm2). After the induction of ischemia in mouse hindlimb ischemic model, immunoflourescent staining showed the expression of membrane-bound E-selectin was noted with maximum expression at 6-12 h. To confirm the key role of membrane-bound E-selectin in homing, blocking antibody to E-selectin was injected locally into the ischemic limb and then mouse EPCs were transplanted systemically. Fluorescent microscopic examination showed a significant reduction of EPC homing to the ischemic limb (n = 8, control vs. blocking = 203 ± 33 vs. 99 ± 35 cells/mm2; P < 0.01). To investigate the effect of rh-E-selectin in vivo, we locally injected rh-E-selectin into athymic ischemic hindlimb muscle of nude mice and then transplanted human EPCs. At day 21 after treatment, higher capillary densities were observed in the rh-E-selectin group (n=8, control vs. rh-E-selectin = 159 ± 26 vs. 250 ± 42 endothelial nuclei/mm2, P < 0.05) and more limb salvage was evident in the rh-E-selectin group (63 %, 5/8) than the control group (33 %, 3/9).
Conclusion: These findings indicate that E-selectin, which is overexpressed in early phase of ischemic tissue, contributes to organ regeneration by augmenting homing and angiogenesis of EPC.
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