Characterization of phosphatidylserine-dependent β2-glycoprotein I macrophage interactions: Implications for apoptotic cell clearance by phagocytes

Krishnakumar Balasubramanian, Alan J. Schroit

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


The binding and uptake of phosphatidylserine (PS)-expressing cells appears to involve multiple receptor-mediated systems that recognize the lipid either directly or indirectly through intermediate proteins that form a molecular bridge between the cells. Here we show that β2-glycoprotein I (β2GPI), a 50-kDa serum glycoprotein, binds PS-containing vesicles and serves as an intermediate for the interaction of these vesicles with macrophages. Chemical modification of lysines and cysteines abolished β2GPI-dependent PS uptake by inhibiting the binding of PS to β2GPI and the binding of PS·β2GPI complex to macrophages, respectively. Recognition was mediated by β2GPI and not by the lipid because antibodies to β2GPI inhibited binding of the complex to macrophages. These results indicate that human (THP-1-derived) macrophages bind β2GPI only after it is bound to its lipid ligand. Competition experiments with monosaccharides that inhibit lectin-dependent interactions, and PS·β2GPI binding experiments using deglycosylated β2GPI, suggested that carbohydrate residues were not required for macrophage recognition of the complex. Antibodies to putative macrophage PS receptors (CD36, CD68, and CD14) did not inhibit uptake of the complex. These data suggest that β2GPI can bind cells that fail to maintain membrane lipid asymmetry and generate a specific bridging moiety that is recognized for clearance by a phagocyte receptor that is distinct from CD36, CD68, and CD14.

Original languageEnglish (US)
Pages (from-to)29272-29277
Number of pages6
JournalJournal of Biological Chemistry
Issue number44
StatePublished - Oct 30 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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