contribution of chondroitin sulfate a to the binding of complement proteins to activated platelets硫酸软骨素的贡献一个绑定的补充蛋白质激活血小板.pdf

Contribution of Chondroitin Sulfate A to the Binding of Complement Proteins to Activated Platelets 1. 2. 3 3 3 1 Osama A. Hamad , Per H. Nilsson , Maria Lasaosa , Daniel Ricklin , John D. Lambris , Bo Nilsson * , Kristina Nilsson Ekdahl1,2 1 Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, Uppsala, Sweden, 2 School of Natural Sciences, Linnaeus University, Kalmar, Sweden, 3 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America Abstract Background: Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. Principal Findings: Human blood serum was passed over Sepharose conjugated with CS-A, and CS-A-specific binding proteins were identified by Western blotting and mass spectrometric analysis. C1q was shown to be the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and then not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were also shown to bind to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to expos