Distinct CD11b+-monocyte subsets accelerate endothelial cell recovery after acute and chronic endothelial cell damage
Distinct CD11b+-monocyte subsets accelerate endothelial cell recovery after acute and chronic endothelial cell damage
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DOI：
10.1016/j.ijcard.2014.02.004
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发表时间：
2014-04-15
影响因子：
3.5
通讯作者：
Werner, Nikos
中科院分区：
文献类型：
--
作者：
Becher, Ulrich M.;Moeller, Lisa;Werner, Nikos
背景：内皮细胞的恢复需要补充内皮谱系的原代细胞。然而，最近的证据表明，先天免疫系统的细胞增强endothelial regeneration.Methods和结果：专注于成熟的CD 11b（+）-单核细胞，我们分析了命运和输注后的CD 11b（+）-单核细胞在体内内皮损伤的影响。CD 11b-白喉毒素受体小鼠-白喉毒素给药选择性消除内源性单核细胞和巨噬细胞的小鼠模型-用来自年龄匹配小鼠的WT来源的CD 11b（+）-单核细胞处理。7天后，CD 11b（+）-单核细胞改善了内皮依赖性血管反应性，而输注WT衍生的CD 11b（-）-细胞对内皮功能没有有益的影响。在患有高胆固醇血症诱导的慢性内皮损伤的ApoE（-/-）-CD 11b-DTR-小鼠中，输注由干扰素-γ（IFN-γ）刺激的WT来源的CD 11b（+）-单核细胞降低了内皮功能，而白细胞介素-4（IL-4）刺激的单核细胞对血管功能没有可检测的影响。生物发光成像显示输注的CD 11b（+）-单核细胞局限于内源性单核细胞耗竭的CD 11b-DTR-小鼠的内皮损伤部位。体外共培养实验显示，与IFN γ刺激的单核细胞相比，与预处理培养基（PCM）或IL 4刺激的单核细胞亚群一起培养时，人内皮生长细胞（EOCs）的再生特性显著增强。CD 11b（+）-单核细胞通过归巢至血管损伤部位，在内皮损伤后的内皮细胞恢复中发挥重要作用，增强再内皮化和改善内皮功能。体外实验表明，IL-4刺激的单核细胞增强EOC再生性能最有可能通过旁分泌诱导增殖和细胞促进分化。这些结果强调了内皮再生生物学的新见解，并为血管功能障碍的治疗提供了额外的信息。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Background: Endothelial cell recovery requires replenishment of primary cells from the endothelial lineage. However, recent evidence suggests that cells of the innate immune system enhance endothelial regeneration.Methods and results: Focusing on mature CD11b(+)-monocytes, we analyzed the fate and the effect of transfused CD11b(+)-monocytes after endothelial injury in vivo. CD11b-diphtheria-toxin-receptor-mice - a mouse model in which administration of diphtheria toxin selectively eliminates endogenous monocytes and macrophages - were treated with WT-derived CD11b(+)-monocytes from age-matched mice. CD11b(+)-monocytes improved endothelium-dependent vasoreactivity after 7 days while transfusion of WT-derived CD11b(-)-cells had no beneficial effect on endothelial function. In ApoE(-/-)-CD11b-DTR-mice with a hypercholesterolemia-induced chronic endothelial injury transfusion of WT-derived CD11b(+)-monocytes stimulated by interferon-gamma (IFN gamma) decreased endothelial function, whereas interleukin-4-stimulated (IL4) monocytes had no detectable effect on vascular function. Bioluminescent imaging revealed restriction of transfused CD11b(+)-monocytes to the endothelial injury site in CD11b-DTR-mice depleted of endogenous monocytes. In vitro co-culture experiments revealed significantly enhanced regeneration properties of human endothelial outgrowth cells (EOCs) when cultured with preconditioned-media (PCM) or monocytes of IL4-stimulated-subsets compared to the effects of IFN gamma-stimulated monocytes.Conclusion: CD11b(+)-monocytes play an important role in endothelial cell recovery after endothelial injury by homing to the site of vascular injury, enhancing reendothelialization and improving endothelial function. In vitro experiments suggest that IL4-stimulated monocytes enhance EOC regeneration properties most likely by paracrine induction of proliferation and cellular promotion of differentiation. These results underline novel insights in the biology of endothelial regeneration and provide additional information for the treatment of vascular dysfunction. (C) 2014 Elsevier Ireland Ltd. All rights reserved.