Bhatwadekar Ashay D, Glenn Josephine V, Curtis Tim M, Grant Maria B, Stitt Alan W, Gardiner Tom A
Centre for Vision Science, Queen's University Belfast, Royal Victoria Hospital, Belfast, Northern Ireland, United Kingdom.
Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4967-73. doi: 10.1167/iovs.09-3616. Epub 2009 May 27.
Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair.
Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed.
Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05-0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-alpha when compared to control medium; SDF-1 remained unchanged.
The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment.
骨髓来源的内皮祖细胞（EPCs）有助于血管修复，尽管目前尚不清楚局部内皮细胞凋亡如何影响其修复功能。本研究旨在确定内皮损伤部位凋亡小体的存在如何影响EPCs参与视网膜微血管修复。
使用光动力药物维替泊芬在视网膜微血管内皮细胞（RMECs）单层中造成凋亡性细胞死亡的微损伤。在凋亡细胞脱离前或从伤口部位移除后，研究早期EPCs对这些损伤的黏附情况。将凋亡小体加入正常RMECs中，并分析黏附分子的mRNA水平。
与凋亡细胞已被移除的损伤相比，凋亡小体留在伤口部位的内皮损伤显示EPC募集增加了五倍（P < 0.05）。在暴露于凋亡小体的完整RMEC单层中，ICAM、VCAM和E-选择素的表达上调了5至15倍（P < 0.05 - 0.001）。EPCs对从凋亡小体获得的条件培养基表现出特征性的趋化反应（P < 0.05），而与对照培养基相比，对培养基的分析显示VEGF、IL-8、IL-6和TNF-α水平显著升高；SDF-1保持不变。
数据表明，源自视网膜毛细血管内皮的凋亡小体介导促血管生成细胞因子和趋化因子的释放，并以促进EPC募集的方式诱导黏附分子表达。
