Autologous Transplantation of Peripheral Blood-derived Circulating Endothelial Progenitor Cells Attenuates Endotoxin-induced Acute Lung Injury in Rabbits by Direct Endothelial Repair and Indirect Immunomodulation

作者：Cao, Jian-Ping; He, Xing-Ying; Xu, Hai-Tao; Zou, Zui; Shi, Xue-Yin^*

来源：Anesthesiology, 2012, 116(6): 1278-1287.

DOI：10.1097/ALN.0b013e3182567f84

• RESPIRATORY-DISTRESS-SYNDROME
• MESENCHYMAL STEM-CELLS
• NITRIC-OXIDE SYNTHASE
• SUPEROXIDE-DISMUTASE
• CRITICALLY-ILL
• ANGIOGENESIS
• MOBILIZATION
• EXPRESSION
• ISCHEMIA
• DISEASES

Background: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin- induced acute lung injury in rabbits and to investigate the underlying mechanisms. @@@ Methods: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. PaO2/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1 beta, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. @@@ Results: PaO2/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1 beta, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. @@@ Conclusions: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.

• 出版日期2012-6
• 单位中国人民解放军第二军医大学; 中国人民解放军第四五五医院; 天津市中医药研究院附属医院