Immune clearance of phosphatidylserine-expressing cells by phagocytes: The role of β2-glycoprotein I in macrophage recognition

Krishnakumar Balasubramanian, Joya Chandra, Alan J. Schroit

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

The function of β2-glycoprotein I (β2GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis (Brighton, T. A., Hogg, P. J., Dai, Y.-P., Murray, B. H., Choing, B. H., and Chesterman, C. N. (1996) Br. J. Haematol. 93, 185-194) and the clearance of phosphatidylserine (PS)- expressing cells (Chonn, A., Semple S.C., and Cullis P. R. (1995) J. Biol. Chem. 270, 25845-25849). To further understand the role of this protein, we characterized the ability of β2GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. β2GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. β2GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was 'shielded' with β2GPI and further increased upon the addition of β2GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bowed β2GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of β2GPI and further increased upon the addition of β2GPI antibodies. It is concluded that β2GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.

Original languageEnglish (US)
Pages (from-to)31113-31117
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number49
DOIs
StatePublished - Dec 5 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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