Phospholipid transfer protein is present in human atherosclerotic lesions and is expressed by macrophages and foam cells.
Phospholipid transfer protein (PLTP) in plasma promotes phospholipid transfer from triglyceride-rich lipoproteins to HDL and plays a major role in HDL remodeling. Recent in vivo observations also support a key role for PLTP in cholesterol metabolism. Our immunohistochemical analysis of human carotid endarterectomy samples identified immunoreactive PLTP in areas that colocalized with CD68-positive macrophages, suggesting that PLTP could be produced locally by intimal macrophages. Using RT-PCR, Western blot analysis with a monoclonal anti-PLTP antibody, and a PLTP activity assay, we observed PLTP mRNA and protein expression in human macrophages. In adherent peripheral blood human macrophages, this PLTP expression was increased by culture with granulocyte macrophage colony-stimulating factor. Incubation of macrophages with acetylated-LDL induced an increase in PLTP mRNA and protein expression that paralleled cholesterol loading. PLTP expression was observed in elicited mouse peritoneal macrophages and in cultured Raw264.7 cells as well. Thus, this study demonstrates that PLTP is expressed by macrophages, is regulated by cholesterol loading, and is present in atherosclerotic lesions.
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Catherine M
CM
Desrumaux
Puiying A
PA
Mak
William A
WA
Boisvert
David
D
Masson
Dwayne
D
Stupack
Matti
M
Jauhiainen
Christian
C
Ehnholm
Linda K
LK
Curtiss
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology; D005487:Foam Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger; D002784:Cholesterol