HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, Q. Articles by Matsuura, E. Search for Related Content PubMed PubMed Citation Articles by Liu, Q. Articles by Matsuura, E. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 43, 1486-1495, September 2002
Copyright © 2002 by Lipid Research, Inc.

-Carboxyl variants of 7-ketocholesteryl esters are ligands for ß₂-glycoprotein I and mediate antibody-dependent uptake of oxidized LDL by macrophages

Qingping Liu^1,*, Kazuko Kobayashi^*, Jun-ichi Furukawa, Junko Inagaki^*, Nobuo Sakairi, Akimasa Iwado, Tatsuji Yasuda^*, Takao Koike^**, Dennis R. Voelker and Eiji Matsuura^2,*

^* Department of Cell Chemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan
Division of Bioscience, Graduate School of Environment Earth Science, Hokkaido University, Sapporo 060-0810, Japan
Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan
^** Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206

² To whom correspondence should be addressed. e-mail: eijimatu{at}md.okayama-u.ac.jp

ß₂-Glycoprotein I (ß₂-GPI) is a major antigen for anticardiolipin antibodies (aCL, Abs) present in patients with antiphospholipid syndrome. We recently reported that ß₂-GPI specifically binds to oxidized LDL (oxLDL) and that the ß₂-GPI's major ligand, oxLig-1 is 7-ketocholesteryl-9-carboxynonanoate (Kobayashi, K., E. Matsuura, Q. P. Liu, J. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, and T. Koike. 2001. A specific ligand for ß₂-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages. J. Lipid Res. 42: 697–709). In the present study, we demonstrate that -carboxylated 7-ketocholesteryl esters are critical for ß₂-GPI binding. A positive ion mass spectrum of a novel ligand, designated oxLig-2, showed fragmented ions at m/z 383 and 441 in the presence of acetone, which share features of oxLig-1 and 7-ketocholesterol. In the negative ion mode, ions at m/z 627, 625, and 243 were observed. oxLig-2 was most likely 7-ketocholesteryl-12-carboxy (keto) dodecanoate. These ligands were recognized by ß₂-GPI. Liposome binding to macrophages was significantly increased depending on the ligand's concentration, in the presence of ß₂-GPI and an anti-ß₂-GPI Ab. Synthesized variant, 7-ketocholesteryl-13-carboxytridecanoate (13-COOH-7KC), also showed a significant interaction with ß₂-GPI and a similar binding profile with macrophages. Methylation of the carboxyl function diminished all of the specific ligand interactions with ß₂-GPI.

Thus, -carboxyl variants of 7-ketocholesteryl esters can mediate anti-ß₂-GPI Ab-dependent uptake of oxLDL by macrophages, and autoimmune atherogenesis linked to ß₂-GPI interaction with oxLDL.

Abbreviations: Ab, antibody; APS, antiphospholipid syndrome; ß₂-GPI, ß₂-glycoprotein I; oxLDL, oxidized LDL; PL, phospholipid; oxLig-1, 7-ketocholesteryl-9-carboxynonanoate; 13-COOH-7KC, 7-ketocholesteryl-13-carboxytridecanoate

Supplementary key words antiphospholipid syndrome • atherosclerosis • autoantibody • ß₂-glycoprotein I • oxidized LDL • -oxidation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E Matsuura and L. Lopez Autoimmune-mediated atherothrombosis Lupus, October 1, 2008; 17(10): 879 - 888. [Abstract] [PDF]

				Y. Yamaguchi, N. Seta, J. Kaburaki, K. Kobayashi, E. Matsuura, and M. Kuwana Excessive exposure to anionic surfaces maintains autoantibody response to 2-glycoprotein I in patients with antiphospholipid syndrome Blood, December 15, 2007; 110(13): 4312 - 4318. [Abstract] [Full Text] [PDF]

				K. Kobayashi, K. Tada, H. Itabe, T. Ueno, P.-H. Liu, A. Tsutsumi, M. Kuwana, T. Yasuda, Y. Shoenfeld, P.G. de Groot, et al. Distinguished effects of antiphospholipid antibodies and anti-oxidized LDL antibodies on oxidized LDL uptake by macrophages Lupus, December 1, 2007; 16(12): 929 - 938. [Abstract] [PDF]

				C. Christodoulou, S. Sangle, and D. P. D'Cruz Vasculopathy and arterial stenotic lesions in the antiphospholipid syndrome Rheumatology, June 1, 2007; 46(6): 907 - 910. [Abstract] [Full Text] [PDF]

				M. Tabuchi, K. Inoue, H. Usui-Kataoka, K. Kobayashi, M. Teramoto, K. Takasugi, K. Shikata, M. Yamamura, K. Ando, K. Nishida, et al. The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis J. Lipid Res., April 1, 2007; 48(4): 768 - 781. [Abstract] [Full Text] [PDF]

				E Matsuura, K Kobayashi, B. Hurley, and L. Lopez Atherogenic Oxidized Low-Density Lipoprotein/{beta}2-Glycoprotein I (oxLDL/{beta}2GPI) Complexes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome Lupus, July 1, 2006; 15(7): 478 - 483. [Abstract] [PDF]

				L R Lopez, M Salazar-Paramo, C Palafox-Sanchez, B L Hurley, E Matsuura, and I Garcia-De La Torre Oxidized low-density lipoprotein and {beta}2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness: implications in autoimmune-mediated atherosclerosis Lupus, February 1, 2006; 15(2): 80 - 86. [Abstract] [PDF]

				E Matsuura, K Kobayashi, K Inoue, L R Lopez, and Y Shoenfeld Oxidized LDL/{beta}2-glycoprotein I complexes: new aspects in atherosclerosis Lupus, September 1, 2005; 14(9): 736 - 741. [Abstract] [PDF]

				E Matsuura, K Kobayashi, T Koike, Y Shoenfeld, M A Khamashta, and G R. Hughes Oxidized low-density lipoprotein as a risk factor of thrombosis in antiphospholipid syndrome Lupus, July 1, 2003; 12(7): 550 - 554. [Abstract] [PDF]