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Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo.

Publication ,  Journal Article
Gui, T; Lin, H-F; Jin, D-Y; Hoffman, M; Straight, DL; Roberts, HR; Stafford, DW
Published in: Blood
July 1, 2002

Residue K5 in factor IX gamma-carboxyglutamic acid (Gla) domain participates in binding endothelial cells/collagen IV. We injected recombinant factor IX containing mutations at residue 5 (K5A, K5R) into factor IX-deficient mice and compared their behavior with that of wild-type factor IX. The plasma concentration of factor IX that binds to endothelial cells/collagen IV (recombinant wild type and K5R) was consistently lower than that of the one that does not bind (K5A). Mice treated with wild type or K5R had 79% of the injected factor IX in the liver after 2 minutes, whereas 17% remained in circulation. In mice injected with K5A, 59% of the injected factor IX was found in liver and 31% was found in plasma. When we blocked the liver circulation before factor IX injection, 74% of K5A and 64% of K5R remained in the blood. When we treated the mouse with EDTA after injecting exogenous factor IX, the blood levels of factor IX that bind to endothelial cells/collagen IV increased, presumably because of release from endothelial cell/collagen IV binding sites. In contrast, the levels of the mutants that do not bind were unaffected by EDTA. In immunohistochemical studies, factor IX appears on the endothelial surfaces of mouse arteries after factor IX injection and of human arteries from surgical specimens. Thus, we have demonstrated that factor IX binds in vivo to endothelial cell-collagen IV surfaces. Our results suggest that factor IX Gla-domain mediated binding to endothelial cells/collagen IV plays a role in controlling factor IX concentration in the blood.

Duke Scholars

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

July 1, 2002

Volume

100

Issue

1

Start / End Page

153 / 158

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Binding
  • Mutation
  • Mice, Knockout
  • Mice
  • Metabolic Clearance Rate
  • Liver
  • Injections
 

Citation

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Gui, T., Lin, H.-F., Jin, D.-Y., Hoffman, M., Straight, D. L., Roberts, H. R., & Stafford, D. W. (2002). Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo. Blood, 100(1), 153–158. https://doi.org/10.1182/blood.v100.1.153
Gui, Tong, Hui-Feng Lin, Da-Yun Jin, Maureane Hoffman, David L. Straight, Harold R. Roberts, and Darrel W. Stafford. “Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo.Blood 100, no. 1 (July 1, 2002): 153–58. https://doi.org/10.1182/blood.v100.1.153.
Gui T, Lin H-F, Jin D-Y, Hoffman M, Straight DL, Roberts HR, et al. Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo. Blood. 2002 Jul 1;100(1):153–8.
Gui, Tong, et al. “Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo.Blood, vol. 100, no. 1, July 2002, pp. 153–58. Pubmed, doi:10.1182/blood.v100.1.153.
Gui T, Lin H-F, Jin D-Y, Hoffman M, Straight DL, Roberts HR, Stafford DW. Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo. Blood. 2002 Jul 1;100(1):153–158.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

July 1, 2002

Volume

100

Issue

1

Start / End Page

153 / 158

Location

United States

Related Subject Headings

  • Tissue Distribution
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Binding
  • Mutation
  • Mice, Knockout
  • Mice
  • Metabolic Clearance Rate
  • Liver
  • Injections