Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
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DOI：
10.1172/jci29968
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发表时间：
2007-03-01
影响因子：
15.9
通讯作者：
Kobzik, Lester
中科院分区：
文献类型：
--
作者：
Dahl, Morten;Bauer, Alison K.;Kobzik, Lester
肺泡巨噬细胞（AMs）表达A类清道夫受体（SRAs），包括具有胶原结构的巨噬细胞受体（MARCO）以及清道夫受体AI/II（SRA - I/II），它们能够识别氧化脂质，并对吸入的病原体和颗粒物提供先天防御。在耐臭氧小鼠的肺部，MARCO表达增加，这表明其在抵御吸入性氧化剂方面具有额外作用。在暴露于臭氧后，MARCO（-/-）小鼠比MARCO（+/+）小鼠表现出更严重的肺损伤。已知臭氧会在肺内衬液中产生具有促炎作用的氧化脂质，例如5β,6β - 环氧胆固醇（β - 环氧化物）和1 - 棕榈酰 - 2 -（9' - 氧代 - 壬酰） - 甘油磷酰胆碱（PON - GPC）。气管内滴注这两种脂质中的任何一种都会导致MARCO（-/-）小鼠大量中性粒细胞流入，但对MARCO（+/+）小鼠没有影响。与MARCO（-/-）肺泡巨噬细胞相比，正常肺泡巨噬细胞在体外对β - 环氧化物的摄取更多，这与SRA结合氧化脂质的功能一致。SRA - I/II（-/-）小鼠在接触β - 环氧化物或另一种吸入性氧化剂（残余燃油飞灰的雾化浸出液）后，表现出类似的急性肺部炎症增强。相比之下，亚急性臭氧暴露并未使SRA - I/II（-/-）小鼠相对于SRA - I/II（+/+）小鼠的炎症增强，这反映了MARCO在肺泡巨噬细胞中的表达增加。这些数据确定了我们所认为的肺泡巨噬细胞清道夫受体在吸入氧化剂后通过清除肺内衬液中的促炎氧化脂质从而减轻肺部炎症的一种新功能。
Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO(-/-) mice showed greater lung injury than did MARCO(+/+) mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5 beta,6 beta-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO(-/-) mice, but had no effect in MARCO(+/+) mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO(-/-) AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI/II+/+ mice, reflecting increased AM expression of MARCO. These data identify what we believe to be a novel function for AM SRAs in decreasing pulmonary inflammation after oxidant inhalation by scavenging proinflammatory oxidized lipids from lung lining fluids.