A host lipase prevents lipopolysaccharide-induced foam cell formation
Jintao Feng,
Wei Jiang,
Xiaofang Cheng,
Benkun Zou,
Alan W. Varley,
Ting Liu,
Guojun Qian,
Wenjiao Zeng,
Jianguo Tang,
Qiang Zhao,
Yiwei Chu,
Yuanyuan Wei,
Xiaobo Li,
Robert S. Munford,
Mingfang Lu
Affiliations
Jintao Feng
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Wei Jiang
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200040, China
Xiaofang Cheng
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Benkun Zou
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Alan W. Varley
Department of Internal Medicine, UT-Southwestern Medical Center at Dallas, Texas 75390, USA
Ting Liu
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Guojun Qian
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Wenjiao Zeng
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Jianguo Tang
Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200040, China
Qiang Zhao
Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China
Yiwei Chu
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Yuanyuan Wei
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Xiaobo Li
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Robert S. Munford
Antibacterial Host Defense Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA
Mingfang Lu
Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200040, China; Corresponding author
Summary: Although microbe-associated molecular pattern (MAMP) molecules can promote cholesterol accumulation in macrophages, the existence of a host-derived MAMP inactivation mechanism that prevents foam cell formation has not been described. Here, we tested the ability of acyloxyacyl hydrolase (AOAH), the host lipase that inactivates gram-negative bacterial lipopolysaccharides (LPSs), to prevent foam cell formation in mice. Following exposure to small intraperitoneal dose(s) of LPSs, Aoah−/− macrophages produced more low-density lipoprotein receptor and less apolipoprotein E and accumulated more cholesterol than did Aoah+/+ macrophages. The Aoah−/− macrophages also maintained several pro-inflammatory features. Using a perivascular collar placement model, we found that Aoah−/− mice developed more carotid artery foam cells than did Aoah+/+ mice after they had been fed a high fat, high cholesterol diet, and received small doses of LPSs. This is the first demonstration that an enzyme that inactivates a stimulatory MAMP in vivo can reduce cholesterol accumulation and inflammation in arterial macrophages.
