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Updated: Oct 20, 2025
Culture of Macrophage Colony-stimulating Factor Differentiated Human Monocyte-derived Macrophages
Published on: June 30, 2016
A host lipase prevents lipopolysaccharide-induced foam cell formation
Jintao Feng1, Wei Jiang1,2, Xiaofang Cheng1
1Department of Immunology, Key Laboratory of Medical Molecular Virology (MOE, NHC, CAMS), School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
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.
Insights
A host enzyme, acyloxyacyl hydrolase (AOAH), inactivates bacterial molecules (LPSs) to prevent cholesterol buildup in macrophages. This study shows AOAH protects against foam cell formation and inflammation in arteries.
Area of Science:
- Immunology
- Molecular Biology
- Cardiovascular Research
Background:
- Microbe-associated molecular patterns (MAMPs) can induce cholesterol accumulation in macrophages, contributing to foam cell formation.
- A host-derived mechanism to inactivate MAMPs and prevent foam cell formation has not been previously described.
Purpose of the Study:
- To investigate the role of acyloxyacyl hydrolase (AOAH), a host lipase, in preventing foam cell formation by inactivating lipopolysaccharides (LPSs).
Main Methods:
- Testing the effect of LPS exposure on macrophages from wild-type and Aoah-deficient mice.
- Utilizing a perivascular collar placement model in mice fed a high-fat, high-cholesterol diet and exposed to LPSs.
Main Results:
- Aoah-deficient macrophages accumulated more cholesterol and exhibited pro-inflammatory features compared to wild-type macrophages after LPS exposure.
- Aoah-deficient mice showed increased carotid artery foam cell formation under conditions of high-fat diet and LPS exposure.
Conclusions:
- Acyloxyacyl hydrolase (AOAH) is a host enzyme that inactivates MAMPs (LPSs) in vivo.
- AOAH plays a critical role in preventing cholesterol accumulation and inflammation in arterial macrophages, thus mitigating foam cell formation.
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