von Willebrand factor is a cofactor in complement regulation.
Several complement proteins interact with hemostatic factors. We discovered that von Willebrand factor (VWF) acts as a cofactor for factor I-mediated cleavage of complement C3b, thereby shutting down complement activation. The complement regulatory function of VWF multimers depends on their size. Smaller VWF multimers enhance cleavage of C3b but large and ultra-large VWF (ULVWF) multimers have no effect on C3b cleavage and permit default complement activation. We conclude that normal plasma VWF multimers prevent complement activation and steer the complement pathway toward generation of inactivated C3b (iC3b). ULVWF multimers, as are present in patients with thrombotic microangiopathy, lack an inhibitory effect on complement and permit complement activation.
Section of Benign Hematology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX;
Shuju
S
Feng
Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX; and.
Xiaowen
X
Liang
Section of Benign Hematology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX;
Michael H
MH
Kroll
Department of Biochemistry, University of Washington, Seattle, WA.
Dominic W
DW
Chung
Section of Benign Hematology, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX;
Vahid
http://orcid.org/0000-0003-2911-1284
V
Afshar-Kharghan
D003167:Complement Activation; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005340:Fibrinogen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D055503:Protein Multimerization; D014841:von Willebrand Factor / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D014841:von Willebrand Factor; D005340:Fibrinogen; D003165:Complement System Proteins