Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells

• DOI: 10.1074/jbc.m109.045427
• Publication Date: 2009-12-02T01:13:50Z
• Authors: Jonatan Leffler; Andrew P. Herbert; Eva Norström; Christoph Q. Schmidt; Paul N. Barlow; Anna M. Blom; Myriam Martin
• Keywords: Jurkat cells; Annexin A2

Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble inhibitors factor H (fH) also recognize apoptotic minimize the pro-inflammatory effects of downstream activation. We used four radiolabeled protein constructs that span different regions 20 control (CCP) modules make up fH found fragments comprising CCPs 6–8, 8–15, 19–20 but not 1–4, bound Jurkat T cells. There possible ligand types on could recruit fH: proteins, carbohydrates, lipids, DNA. 6–8 bind annexin-II, a trypsin-insensitive becomes exposed surfaces The second fH, interacts with 19–20, is Confocal microscopy showed co-localization antibodies specific for binds histones devoid DNA, 8–15 mediate this interaction. Treatment neuraminidase, chondroitinase, heparitinase, heparinase did change binding. phospholipase A2 dramatically increased both binding cell-surface excluded possibility lysophospholipids using surface plasmon resonance flow cytometry lipid-coated beads. Identification annexin-II one ligands together fact autoantibodies against in systemic lupus erythematosus provides further insight into understanding pathogenesis disease.