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Journal of Lipid Research, Vol. 44, 1453-1461, August 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Phospholipid transfer protein is present in human atherosclerotic lesions and is expressed by macrophages and foam cells

Catherine M. Desrumaux^*, Puiying A. Mak, William A. Boisvert^*, David Masson, Dwayne Stupack^*, Matti Jauhiainen^**, Christian Ehnholm^** and Linda K. Curtiss^1,*

^* Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Department of Biological Chemistry and Medicine, University of California, Los Angeles, CA 90095
Laboratoire de Biochimie des Lipoprotéines, INSERM U498, Dijon, France
^** Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

¹ To whom correspondence should be addressed. e-mail: lcurtiss{at}scripps.edu

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.

Abbreviations: ABCA1, ATP binding cassette transporter A1; Ac-LDL, acetylated LDL; CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; FC, free cholesterol; GM-CSF, granulocyte macrophage colony-stimulating factor; LPDS, lipoprotein-deficient serum; LPL, lipoprotein lipase; PLTP, phospholipid transfer protein

Supplementary key words atherosclerosis • lipoproteins • lipid transfer

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