title: The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A.
abstract: Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with (3)H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. (3)H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of (3)H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36% (P < 0.05) and 80% (P < 0.001), respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived (3)H-cholesterol in bile, and fecal excretion was reduced by only 45% (P < 0.05). Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment.
authors: Saha Cardiovascular Research Center, University of Kentucky Medical Center, Lexington, KY 40536, USA ; Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536, USA.
authors: Maria C
authors: MC
authors: de Beer
authors: Joanne M
authors: JM
authors: Wroblewski
authors: Victoria P
authors: VP
authors: Noffsinger
authors: Ailing
authors: A
authors: Ji
authors: Jason M
authors: JM
authors: Meyer
authors: Deneys R
authors: DR
authors: van der Westhuyzen
authors: Frederick C
authors: FC
authors: de Beer
authors: Nancy R
authors: NR
authors: Webb