缺血再灌注損傷是無(wú)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(xiǎn)因素。盡管中性粒細(xì)胞是急性肺損傷的關(guān)鍵介質(zhì)，但指導(dǎo)其進(jìn)入肺組織的過(guò)程尚不清楚。在這里，我們發(fā)現(xiàn) CCR2⁺經(jīng)典單核巨噬細(xì)胞對(duì)于在肺門(mén)夾閉或肺移植后缺血再灌注損傷期間介導(dǎo)中性粒細(xì)胞外滲到肺組織中是必要且足夠的。經(jīng)典單核細(xì)胞從宿主脾臟動(dòng)員，脾切除術(shù)減弱了經(jīng)典單核細(xì)胞的募集以及中性粒細(xì)胞進(jìn)入受傷肺組織，這與移植物功能的改善有關(guān)。中性粒細(xì)胞外滲是由移植物浸潤(rùn)經(jīng)典單核細(xì)胞產(chǎn)生 MyD88 依賴(lài)性 IL-1β 介導(dǎo)的，該單核細(xì)胞下調(diào)了肺血管內(nèi)皮細(xì)胞中緊密連接相關(guān)蛋白 ZO-2 的表達(dá)。因此，我們揭示了從脾臟動(dòng)員的經(jīng)典單核細(xì)胞在介導(dǎo)中性粒細(xì)胞外滲的關(guān)鍵作用，對(duì)靶向受體經(jīng)典單核細(xì)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(chēng)：J Clin Invest.

時(shí)間期卷：2018;128(7):2833–2847

在線(xiàn)時(shí)間：2018年5月21日

DOI：doi.org/10.1172/JCI98436.

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱(chēng)：Clodronate Liposomes and Control Liposomes