Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury.
Lectin-like oxidized low-density lipoprotein receptor 1 attenuates pneumonia-induced lung injury.
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DOI：
10.1172/jci.insight.149955
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发表时间：
2022-12-08
期刊：
影响因子：
8
通讯作者：
Quinton, Lee J.
中科院分区：
文献类型：
--
作者：
Korkmaz, Filiz T.;Shenoy, Anukul T.;Symer, Elise M.;Baird, Lillia A.;Odom, Christine V.;Arafa, Emad I.;Na, Elim;Dimbo, Ernest L.;Molina-Arocho, William;Brudner, Matthew;Standiford, Theodore J.;Mehta, Jawahar L.;Sawamura, Tatsuya;Jones, Matthew R.;Mizgerd, Joseph P.;Traber, Katrina E.;Quinton, Lee J.
确定导致肺炎发病率和严重程度的宿主因素对于指导开发更有效的治疗方法至关重要。凝集素样氧化低密度脂蛋白受体1（LOX-1，由OLR 1编码）是一种清道夫受体，已知可促进血管损伤和炎症，但LOX-1是否以及如何在肺中发挥作用尚不清楚。在这里，我们提供了LOX-1在急性呼吸窘迫综合征患者和肺炎小鼠肺部大量积累的证据。与先前描述的LOX-1的损伤性贡献不同，我们发现LOX-1在肺气隙中具有独特的保护作用，限制蛋白质性水肿和炎症。我们还鉴定了肺泡巨噬细胞和募集的嗜中性粒细胞作为肺中LOX-1表达的2个显著位点，由此巨噬细胞能够在肺炎期间进一步诱导，而嗜中性粒细胞在感染的肺中表现出LOX-1的快速但异质的升高。LOX-1的阻断导致肺泡巨噬细胞中免疫信号的失调，其特征在于活化标志物的改变和伴随的炎症基因网络的升高。然而，骨髓嵌合体也表明了在LOX-1介导的肺保护中中性粒细胞的突出作用，进一步支持LOX-1+中性粒细胞表现出与修复过程一致的转录变化。总之，这项工作确立了LOX-1作为肺炎期间肺中的组织保护因子，可能是通过其对肺泡巨噬细胞和LOX-1+气隙中性粒细胞中的免疫信号传导的影响介导的。
Identifying host factors that contribute to pneumonia incidence and severity are of utmost importance to guiding the development of more effective therapies. Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1, encoded by OLR1) is a scavenger receptor known to promote vascular injury and inflammation, but whether and how LOX-1 functions in the lung are unknown. Here, we provide evidence of substantial accumulation of LOX-1 in the lungs of patients with acute respiratory distress syndrome and in mice with pneumonia. Unlike previously described injurious contributions of LOX-1, we found that LOX-1 is uniquely protective in the pulmonary airspaces, limiting proteinaceous edema and inflammation. We also identified alveolar macrophages and recruited neutrophils as 2 prominent sites of LOX-1 expression in the lungs, whereby macrophages are capable of further induction during pneumonia and neutrophils exhibit a rapid, but heterogenous, elevation of LOX-1 in the infected lung. Blockade of LOX-1 led to dysregulated immune signaling in alveolar macrophages, marked by alterations in activation markers and a concomitant elevation of inflammatory gene networks. However, bone marrow chimeras also suggested a prominent role for neutrophils in LOX-1–mediated lung protection, further supported by LOX-1+ neutrophils exhibiting transcriptional changes consistent with reparative processes. Taken together, this work establishes LOX-1 as a tissue-protective factor in the lungs during pneumonia, possibly mediated by its influence on immune signaling in alveolar macrophages and LOX-1+ airspace neutrophils.
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影响因子：
39.3
作者：
Akhmedov, Alexander;Rozenberg, Izabela;Luescher, Thomas F.
通讯作者：
Luescher, Thomas F.
影响因子：
20.1
作者：
Mehta, Jawahar L.;Sanada, Nobuhito;Sawamura, Tatsuya
通讯作者：
Sawamura, Tatsuya
影响因子：
5
作者：
Hu, Changping;Chen, Jiawei;Mehta, Jawahar L.
通讯作者：
Mehta, Jawahar L.
DOI：
10.1007/s12265-015-9655-z
发表时间：
2015-11-01
影响因子：
3.4
作者：
De Siqueira, Jonathan;Zani, Izma Abdul;Homer-Vanniasinkam, Shervanthi
通讯作者：
Homer-Vanniasinkam, Shervanthi
影响因子：
8
作者：
Arafa EI;Shenoy AT;Barker KA;Etesami NS;Martin IM;Lyon De Ana C;Na E;Odom CV;Goltry WN;Korkmaz FT;Wooten AK;Belkina AC;Guillon A;Forsberg EC;Jones MR;Quinton LJ;Mizgerd JP
通讯作者：
Mizgerd JP