Lipopolysaccharide Decreases Scavenger Receptor mRNAIn Vivo

Lipopolysaccharide (LPS) downregulates scavenger receptor (ScR) activity in cultured macrophages through release of tumor necrosis factor-α (TNF-α). However, LPS administration in vivo stimulates cytokine release from both macrophages and lymphocytes, the combined effects of which could alter ScR expression differently from TNF-α in isolation. To investigate whether LPS regulates ScR in vivo, 10 μg/g was injected i.p. into Swiss Webster mice. Administration of LPS produced a profound decrease in hepatic ScR mRNA, with reductions of 74% ± 8% at 2 h that returned to baseline levels by 6 h. Changes in ScR mRNA abundance coincided with changes in serum concentrations of TNF-α, which peaked at 2 h (1320 ± 309 pg/ml) and returned to preinjection concentrations at 4 h. Serum concentrations of interferon-γ (IFN-γ) did not increase until 4 h after injection of LPS. There was no effect on ScR mRNA abundance following LPS administration to LPS-resistant strains of mice, C3H/HeJ and IFN-γ receptor-/-. The LPS-induced reduction in ScR mRNA in Swiss Webster mice was not sufficiently sustained to affect receptor function, as determined by the kinetics of [125I]-acetylated LDL clearance from plasma. Therefore, as observed in cultured cells, LPS administration to mice decreases ScR mRNA despite the release of several cytokines in vivo.