title: Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes.
abstract: The molecular linkage between ultralarge (UL) von Willebrand factor (VWF) multimers and the alternative complement pathway (AP) has recently been described. Endothelial cell (EC)-secreted and anchored ULVWF multimers (in long stringlike structures) function as both hyperadhesive sites that initiate platelet adhesion and aggregation and activating surfaces for the AP. In vitro, the active form of C3, C3b binds to the EC-anchored ULVWF multimeric strings and initiates the assembly on the strings of C3 convertase (C3bBb) and C5 convertase (C3bBbC3b). In vivo, activation of the AP via this mechanism proceeds all the way to generation of terminal complement complexes (C5b-9).
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Turner
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA; Section of Hematology-Oncology, Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, 6701 Fannin St., Houston, TX 77004, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Sartain
authors.affiliation: Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA. Electronic address: jmoake@rice.edu.
authors.forename: Joel
authors.initials: J
authors.lastname: Moake
mesh_terms: D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D015539:Platelet Activation / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology* / Q000378:metabolism; D014841:von Willebrand Factor / Q000276:immunology* / Q000378:metabolism
chemical_list: D003176:Complement C3; D014841:von Willebrand Factor
keywords: Alternative complement pathway; Factor H; Thrombotic microangiopathies; VWF