Streptococcal Serum Opacity Factor Increases the Rate of Hepatocyte Uptake of Human Plasma High-Density Lipoprotein Cholesterol

Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that co...

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Published in:Biochemistry (Easton) 2010-11, Vol.49 (45), p.9866-9873
Main Authors: Gillard, Baiba K, Rosales, Corina, Pillai, Biju K, Lin, Hu Yu, Courtney, Harry S, Pownall, Henry J
Format: Article
Language:English
Subjects:
Animals
Boron Compounds - metabolism
Cell Culture Techniques
CHO Cells - metabolism
Cholesterol Esters - metabolism
Cholesterol, HDL - drug effects
Cholesterol, HDL - metabolism
Cricetinae
Cricetulus
Hepatocytes - cytology
Hepatocytes - drug effects
Hepatocytes - metabolism
Humans
Kinetics
Liver - metabolism
Microscopy, Confocal
Peptide Hydrolases - pharmacology
Streptococcus pyogenes - metabolism
Streptococcus pyogenes - pathogenicity
Virulence
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Summary:Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [3H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[3H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[3H]CE uptake by both receptors. RAP and heparin inhibit CERM-[3H]CE but not HDL-[3H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi101412m