Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes

Nancy Turner; Sarah Sartain; Joel Moake

doi:10.1016/j.hoc.2015.01.008

Ultralarge von Willebrand factor-induced platelet clumping and activation of the alternative complement pathway in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndromes

Hematol Oncol Clin North Am. 2015 Jun;29(3):509-24. doi: 10.1016/j.hoc.2015.01.008. Epub 2015 Mar 12.

Authors

Nancy Turner¹, Sarah Sartain², Joel Moake³

Affiliations

¹ Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA.
² 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.
³ Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, USA. Electronic address: jmoake@rice.edu.

PMID: 26043389
DOI: 10.1016/j.hoc.2015.01.008

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).

Keywords: Alternative complement pathway; Factor H; Thrombotic microangiopathies; VWF.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Complement C3 / immunology
Complement C3 / metabolism
Complement Pathway, Alternative / immunology*
Endothelial Cells / immunology
Endothelial Cells / metabolism
Hemolytic-Uremic Syndrome / immunology*
Hemolytic-Uremic Syndrome / metabolism
Humans
Models, Immunological
Platelet Activation / immunology*
Platelet Aggregation / immunology*
Purpura, Thrombotic Thrombocytopenic / immunology*
Purpura, Thrombotic Thrombocytopenic / metabolism
von Willebrand Factor / immunology*
von Willebrand Factor / metabolism

Substances

Complement C3
von Willebrand Factor