Apolipoprotein modulation of streptococcal serum opacity factor activity against human plasma high-density lipoproteins.
Human plasma HDL are the target of streptococcal serum opacity factor (SOF), a virulence factor that clouds human plasma. Recombinant (r) SOF transfers cholesteryl esters (CE) from approximately 400,000 HDL particles to a CE-rich microemulsion (CERM), forms a cholesterol-poor HDL-like particle (neo HDL), and releases lipid-free (LF) apo A-I. Whereas the rSOF reaction requires labile apo A-I, the modulation effects of other apos are not known. We compared the products and rates of the rSOF reaction against human HDL and HDL from mice overexpressing apos A-I and A-II. Kinetic studies showed that the reactivity of various HDL species is apo-specific. LpA-I reacts faster than LpA-I/A-II. Adding apos A-I and A-II inhibited the SOF reaction, an effect that was more profound for apo A-II. The rate of SOF-mediated CERM formation was slower against HDL from mice expressing human apos A-I and A-II than against WT mice HDL and slowest against HDL from apo A-II overexpressing mice. The lower reactivity of SOF against HDL containing human apos is due to the higher hydropathy of human apo A-I, particularly its C-terminus relative to mouse apo A-I, and the higher lipophilicity of human apo A-II. The SOF-catalyzed reaction is the first to target HDL rather than its transporters and receptors in a way that enhances reverse cholesterol transport (RCT). Thus, effects of apos on the SOF reaction are highly relevant. Our studies show that the "humanized" apo A-I-expressing mouse is a good animal model for studies of rSOF effects on RCT in vivo.
Rosales
Corina
C
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Gillard
Baiba K
BK
Courtney
Harry S
HS
Blanco-Vaca
Francisco
F
Pownall
Henry J
HJ
D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016633:Apolipoprotein A-II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002384:Catalysis; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D002788:Cholesterol Esters / Q000378:metabolism; D004655:Emulsions; D006801:Humans; D008075:Lipoproteins, HDL / Q000037:antagonists & inhibitors* / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D010447:Peptide Hydrolases / Q000097:blood* / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000502:physiology*
C505693:APOA1 protein, human; C115794:APOA2 protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D004655:Emulsions; D008075:Lipoproteins, HDL; D010446:Peptide Fragments; D011994:Recombinant Proteins; C021908:opacity factor; D010447:Peptide Hydrolases