LFA-1和VLA-4参与人高增殖潜能内皮祖细胞与血管内皮的黏附和跨内皮迁移

LFA-1 and VLA-4 Involved in Vasoendothelial Adhesion and Transendothelial Migration of Human High Proliferative Potential Endothelial Progenitor Cells

为了了解淋巴细胞功能相关抗原1(lymphocyte function-associated antigen 1,LFA-1)和极迟反应抗原4(very late antigen 4,VLA-4)在高增殖潜能内皮祖细胞(high proliferative potential endothelial progenitor cells,HPP-EPCs)归巢过程中与血管内皮的黏附和跨内皮迁移中的作用,利用流式细胞术检测HPP-EPC中整合蛋白β1和β2的表达以及小鼠骨髓内皮细胞相应的受体的表达。利用体外黏附和迁移实验研究经过功能级别的中和抗体阻断VLA-4和LFA-1后HPP-EPC黏附和迁移细胞数目的变化。结果表明,HPP-EPC表达整合蛋白β1和β2,活化后小鼠骨髓内皮细胞表达细胞间黏附分子1(intercellular adhesion molecule 1,ICAM-1)和血管细胞黏附分子1(vascular cell adhesion molecule 1,VCAM-1);加CD11a抗体组黏附细胞或CD49d抗体组黏附和迁移细胞均较同型对照抗体组少,而且加CD11a和CD49d两种抗体联用组黏附和迁移细胞明显减少,其细胞数较任何单一抗体组少。结论:LFA-1和VLA-4在HPP-EPC与血管内皮的黏附和跨内皮迁移中发挥了重要的作用。

To investigate whether lymphocyte function-associated antigen 1 （ LFA-1 ） and very late antigen 4 （ VLA- 4） are involved in vasoendothelial adhesion and transendothelial migration of high proliferative potential endothelial progenitor cells （HPP-EPCs）, flow cytometry was used to analyze the expression of integrin β1 and β2, the expression of intercellular adhesion molecule （ ICAM-1, 2 ） and vascular cell adhesion molecule （ VCAM-1 ） in mouse bone marrow endothelial cells （mBMECs）. The adhesion and transmigration through endothelial cells of the HPP-EPCs blocked by functional grade neutralizing antibodies of VLA-4 and LFA-1 were studied in vitro. The results revealed that HPP-EPCs were positive for CD1 la and CD49d in HPP-EPCs. The expression of ICAM-land VCAM-1 of mBMECs increased after activated by IL-1β and TNF-α. The results of adhesion in vitro revealed that the numbers of the adhered and migrated cells in the CD11a antibody group, in the CD49d antibody group and in the combinational antibody group were less than those in the isotype control antibody group. Furthermore, the number of adhered and migrated cells in the combinational antibody group was less than that in the CD11 a or the CD49d antibody group （ p 〈 0.05 ）. It is concluded that both LFA- 1 and VLA-4 are involved in vasoendothelial adhesion and transendothelial migration of HPP-EPCs.