VLA-4和LFA-1参与HPP-EPC体内向缺血组织的归巢

The role of VLA-4 and LFA-1 in homing of high proliferative potential endothelial progenitor cells into ischemic tissue

目的研究极迟反应抗原(VLA-4)和淋巴细胞功能抗原(LFA-1)参与高增殖潜能内皮祖细胞(HPP-EPC)体内向缺血组织的归巢的情况。方法结扎股动脉构建裸鼠后肢缺血模型,移植经功能级别的VLA-4(或CD49d)和LFA-1(或CD11a)中和抗体阻断后的HPP-EPCs,观察肢体坏死长度和肢体脱失情况,用放射性核素方法检测缺血肢体血流恢复程度,组织学方法计数毛细血管密度和归巢到缺血区肌肉组织的荧光标记的内皮祖细胞数目。结果CD11a抗体组、CD49d抗体组及两种抗体联用组的肢体坏死长度都较同型对照抗体组为高(P<0.05)。而且,两种抗体联用组比任一种抗体组的肢体坏死长度都要高(P<0.05)。各抗体阻滞组血流恢复、毛细血管密度和归巢HPP-EPC细胞数目均较同型对照抗体封闭组低(P<0.05)。而且,两种抗体联用组比任一种抗体组的肢体血流、毛细血管密度和归巢HPP-EPC细胞数目改善都明显(P<0.05)。结论LFA-1和VLA-4参与了HPP-EPC体内向缺血组织的归巢过程。

Objective To investigate the role of very late antigen （ VLA - 4） and lymphocyte function - associated anti- gen （ LFA - 1 ） in homing of high proliferative potential endothelial progenitor cells （ HPP - EPC ） into ischemic tissue. Methods The mouse models of ischemia were established and were transfused with HPP - EPCs labeled with CM - DiI and blocked by functional grade neutralizing antibodies of VLA - 4 and LFA - 1. The loss of limbs was observed and the length of necrosis limbs was measured. The blood flow of limb was analyzed by radionuclide examination. And the capillary density and the number of EPCs resided in ischemic muscles were analyzed by microscopy. Results The pre - incubation of HPP - EPCs with neutralizing antibodies against CD11 a or CD49d reduced recovery of hind - limb blood flow, capillary density and incorporation of HPP - EPC into ischemic tissues in vivo. Furthermore, the pre - incubation of HPP - EPCs with the combination of CDlla and CD49d ant/bodies led to synergistically negative effects on the homing of HPP - EPCs to ischemic tissue and on neovascularization capacity in vivo. Conclusion Both LFA - 1 and VLA - 4 are involved in H-PP - EPCs homing to ischemic tissue.