A host lipase prevents lipopolysaccharide-induced foam cell formation

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.