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

doi:10.1016/j.isci.2021.103004

A host lipase prevents lipopolysaccharide-induced foam cell formation

iScience. 2021 Aug 19;24(9):103004. doi: 10.1016/j.isci.2021.103004. eCollection 2021 Sep 24.

Authors

Jintao Feng¹, Wei Jiang^{1

2}, Xiaofang Cheng¹, Benkun Zou¹, Alan W Varley³, Ting Liu¹, Guojun Qian¹, Wenjiao Zeng⁴, Jianguo Tang², Qiang Zhao⁵, Yiwei Chu¹, Yuanyuan Wei¹, Xiaobo Li⁶, Robert S Munford⁷, Mingfang Lu^{1

2}

Affiliations

¹ Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
² Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200040, China.
³ Department of Internal Medicine, UT-Southwestern Medical Center at Dallas, Texas 75390, USA.
⁴ Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
⁵ Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China.
⁶ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
⁷ 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.

Abstract

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.

Keywords: cell biology; lipid; molecular biology.

Grants and funding

R01 AI018188/AI/NIAID NIH HHS/United States