Studies on the Basis for the Properties of Fibrin Produced from Fibrinogen-Containing γ′ Chains

Authors

Kevin R. Siebenlist, Marquette UniversityFollow
Michael W. Mosesson, Blood Center of WisconsinFollow
Irene Hernandez, Washington University School of Medicine in St. LouisFollow
Leslie A. Bush, Cleveland State University
Enrico Di Cera, Baxter Healthcare Corp.
John R. Shainoff, Baxter Healthcare Corp.
James P. DiOrio, Baxter Healthcare Corp.Follow
Laurie Stajanovic, Baxter Healthcare Corp.

Document Type

Article

Language

eng

Format of Original

7 p.

Publication Date

10-15-2005

Publisher

American Society of Hematology

Source Publication

Blood

Source ISSN

0006-4971

Original Item ID

doi: 10.1182/blood-2005-01-0240

Abstract

Human fibrinogen 1 is homodimeric with respect to its γ chains (`γ_A-γ_A'), whereas fibrinogen 2 molecules each contain one γ_A (γ_A1-411V) and one γ' chain, which differ by containing a unique C-terminal sequence from γ'408 to 427L that binds thrombin and factor XIII. We investigated the structural and functional features of these fibrins and made several observations. First, thrombin-treated fibrinogen 2 produced finer, more branched clot networks than did fibrin 1. These known differences in network structure were attributable to delayed release of fibrinopeptide (FP) A from fibrinogen 2 by thrombin, which in turn was likely caused by allosteric changes at the thrombin catalytic site induced by thrombin exosite 2 binding to the γ' chains. Second, cross-linking of fibrin γ chains was virtually the same for both types of fibrin. Third, the acceleratory effect of fibrin on thrombin-mediated XIII activation was more prominent with fibrin 1 than with fibrin 2, and this was also attributable to allosteric changes at the catalytic site induced by thrombin binding to γ' chains. Fourth, fibrinolysis of fibrin 2 was delayed compared with fibrin 1. Altogether, differences between the structure and function of fibrins 1 and 2 are attributable to the effects of thrombin binding to γ' chains.

Comments

Accepted version. Blood, Vol. 106, No. 8 (October 15, 2005): 2730-2736. DOI. © 2005 American Society of Hematology (ASH). Used with permission.

Recommended Citation

Siebenlist, Kevin R.; Mosesson, Michael W.; Hernandez, Irene; Bush, Leslie A.; Cera, Enrico Di; Shainoff, John R.; DiOrio, James P.; and Stajanovic, Laurie, "Studies on the Basis for the Properties of Fibrin Produced from Fibrinogen-Containing γ′ Chains" (2005). Biomedical Sciences Faculty Research and Publications. 41.
https://epublications.marquette.edu/biomedsci_fac/41