期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 117, 期 3, 页码 757-764出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI29968
关键词
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资金
- NIEHS NIH HHS [K22 ES014731-01, ES00002, R01 ES011008, P30 ES000002, K22 ES014731, ES011008] Funding Source: Medline
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.
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