Clodronate Liposomes助力脾来源经典单核细胞以IL-1β介导肺缺血再灌注损伤研究
时间:2025-01-08 阅读:111
中文摘要:
缺血再灌注损伤是无菌性炎症的一种形式,是肺移植术后短期死亡和慢性肺同种异体移植物功能障碍的主要危险因素。尽管中性粒细胞是急性肺损伤的关键介质,但指导其进入肺组织的过程尚不清楚。在这里,我们发现 CCR2+经典单核巨噬细胞对于在肺门夹闭或肺移植后缺血再灌注损伤期间介导中性粒细胞外渗到肺组织中是必要且足够的。经典单核细胞从宿主脾脏动员,脾切除术减弱了经典单核细胞的募集以及中性粒细胞进入受伤肺组织,这与移植物功能的改善有关。中性粒细胞外渗是由移植物浸润经典单核细胞产生 MyD88 依赖性 IL-1β 介导的,该单核细胞下调了肺血管内皮细胞中紧密连接相关蛋白 ZO-2 的表达。因此,我们揭示了从脾脏动员的经典单核细胞在介导中性粒细胞外渗的关键作用,对靶向受体经典单核细胞以改善临床上肺缺血再灌注损伤具有潜在意义。
英文摘要:
Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation. The classical monocytes were mobilized from the host spleen, and splenectomy attenuated the recruitment of classical monocytes as well as the entry of neutrophils into injured lung tissue, which was associated with improved graft function. Neutrophil extravasation was mediated by MyD88-dependent IL-1β production by graft-infiltrating classical monocytes, which downregulated the expression of the tight junction–associated protein ZO-2 in pulmonary vascular endothelial cells. Thus, we have uncovered a crucial role for classical monocytes, mobilized from the spleen, in mediating neutrophil extravasation, with potential implications for targeting of recipient classical monocytes to ameliorate pulmonary ischemia-reperfusion injury in the clinic.
论文信息:
论文题目: Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β
期刊名称:J Clin Invest.
时间期卷:2018;128(7):2833–2847
在线时间:2018年5月21日
DOI:doi.org/10.1172/JCI98436.
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes and Control Liposomes
办事处:Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体助力肺脏缺血再灌注损伤(IR)模型巨噬细胞研究,荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于JCI:
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法: