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

作　　者：段华新[1] 卢光琇[2] 程腊梅[2] 

机构地区：[1]广州医学院附属广州市第一人民医院血液科,广东广州510180 [2]中南大学生殖与干细胞工程研究所人类干细胞国家工程研究中心,湖南长沙410078

出　　处：《中国热带医学》2008年第9期1475-1478,共4页China Tropical Medicine

基　　金：国家863项目基金(编号:2003AA205181);国家973项目基金(编号:00CB51010);国家自然科学基金重点项目(编号:30030070);中国博士后项目基金(编号:20070420762);湖南省自然科学基金(编号:07JJ5034);广东省医学科学技术研究基金(编号:A2008519);广州市医药卫生科技项目(编号:2007 -YB -003)资助

摘　　要：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.

关 键 词：高增殖潜能内皮祖细胞 极迟反应抗原 淋巴细胞功能抗原 归巢 机制 

分 类 号：R364.3[医药卫生—病理学]