缺血再灌注損傷是無菌性炎癥的一種形式，是肺移植術(shù)后短期死亡和慢性肺同種異體移植物功能障礙的主要危險因素。盡管中性粒細胞是急性肺損傷的關(guān)鍵介質(zhì)，但指導(dǎo)其進入肺組織的過程尚不清楚。在這里，我們發(fā)現(xiàn) CCR2⁺經(jīng)典單核巨噬細胞對于在肺門夾閉或肺移植后缺血再灌注損傷期間介導(dǎo)中性粒細胞外滲到肺組織中是必要且足夠的。經(jīng)典單核細胞從宿主脾臟動員，脾切除術(shù)減弱了經(jīng)典單核細胞的募集以及中性粒細胞進入受傷肺組織，這與移植物功能的改善有關(guān)。中性粒細胞外滲是由移植物浸潤經(jīng)典單核細胞產(chǎn)生 MyD88 依賴性 IL-1β 介導(dǎo)的，該單核細胞下調(diào)了肺血管內(nèi)皮細胞中緊密連接相關(guān)蛋白 ZO-2 的表達。因此，我們揭示了從脾臟動員的經(jīng)典單核細胞在介導(dǎo)中性粒細胞外滲的關(guān)鍵作用，對靶向受體經(jīng)典單核細胞以改善臨床上肺缺血再灌注損傷具有潛在意義。

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.

論文信息：

論文題目： Spleen-derived classical monocytes mediate lung ischemia-reperfusion injury through IL-1β

期刊名稱：J Clin Invest.

時間期卷：2018;128(7):2833–2847

在線時間：2018年5月21日

DOI：doi.org/10.1172/JCI98436.

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes