A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice

eLife

Wei Jiang¹  Benkun Zou¹  Yiwei Chu¹  Mingfang Lu²  Jianguo Tang³  Robert S Munford⁴  Danial Saleem⁴  Michael Goodwin⁴ 

[1]Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences & Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

[2]Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences & Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China

[3]Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

[4]Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China

[5]Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, United States

关键词: acyloxyacyl hydrolase;    oxidized phospholipid;    macrophage;    inflammasome;    acute lung injury;    Mouse;   

DOI  :  10.7554/eLife.70938

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Oxidized phospholipids have diverse biological activities, many of which can be pathological, yet how they are inactivated in vivo is not fully understood. Here, we present evidence that a highly conserved host lipase, acyloxyacyl hydrolase (AOAH), can play a significant role in reducing the pro-inflammatory activities of two prominent products of phospholipid oxidation, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine. AOAH removed the sn-2 and sn-1 acyl chains from both lipids and reduced their ability to induce macrophage inflammasome activation and cell death in vitro and acute lung injury in mice. In addition to transforming Gram-negative bacterial lipopolysaccharide from stimulus to inhibitor, its most studied activity, AOAH can inactivate these important danger-associated molecular pattern molecules and reduce tissue inflammation and injury.

【 授权许可】

CC BY