Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-β2 glycoprotein I antibodies. (October 2016)

• Record Type: Journal Article
• Authors: Otomo, K; Amengual, O; Fujieda, Y; Nakagawa, H; Kato, M; Oku, K; Horita, T; Yasuda, S; Matsumoto, M; Nakayama, K I; Hatakeyama, S; Koike, T; Atsumi, T
• Is Part Of: Lupus. Volume 25:Number 12(2016)
• Page Start: 1288
• Page End: 1298
• Publication Date: 2016-10
• Subjects: Apolipoprotein B100 -- anticardiolipin antibody -- beta2-glycoprotein I -- lipoprotein-associated phospholipase A2 -- oxidized LDL -- tissue factor; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1177/0961203316638165
• Languages: English
• ISSNs: 0961-2033

Abstract

Objective: The objective of this paper is to elucidate the not yet known plasma molecule candidates involved in the induction of tissue factor (TF) expression mediated by β2GPI-dependent anticardiolipin antibody (aCL/β2GPI) on monocytes. Methods: Human serum incubated with FLAG-β2GPI was applied for affinity chromatography with anti- FLAG antibody. Immunopurified proteins were analyzed by a liquid chromatography coupled with mass spectrometry (LC-MS). TF mRNA induced by the identified molecules on monocytes was also analyzed. Results: Apolipoprotein B100 (APOB) was the only identified serum molecule in the MS search. Oxidized LDL, containing APOB as well as ox-Lig1 (a known ligand of β2GPI), was revealed as a β2GPI-binding molecule in the immunoprecipitation assay. TF mRNA was markedly induced by oxidized LDL/β2GPI complexes with either WBCAL-1 (monoclonal aCL/β2GPI) or purified IgG from APS patients. The activities of lipoprotein-associated phospholipase A2, one of the component molecules of oxidized LDL, were significantly higher in serum from APS patients than in those from controls. Conclusion: APOB (or oxidized LDL) was detected as a major β2GPI binding serum molecule by LC-MS search. Oxidized LDL/aCL/β2GPI complexes significantly induced TF expressions on monocytes. These data suggest that complexes of oxidized LDL and aCL/β2GPI may have a crucial role in the pathophysiology of APS.