Factor V turnover in a primate model
MD Rand, SR Hanson and KG Mann
Department of Biochemistry, University of Vermont, College of Medicine,
Burlington 05405-0068, USA.
The isolation and characterization of baboon plasma factor V (FV) were
performed for the development of an in vivo model for studying factor V/Va
physiology in nonhuman primates. Baboon FV was purified by immunoaffinity
chromatography with an antihuman FV monoclonal antibody and exhibits a
specific activity of 1,940 U/mg. Baboon FV activation by thrombin proceeds
through two proteolytic pathways similar to those observed with human and
bovine FV. Limited amino acid sequencing of FV and its thrombin activation
fragments shows 95% identity with human and 79% identity with bovine FV.
125I-Factor V and a mixture of thrombin cleaved 125I-FV activation products
were infused into normal male baboons and evaluated by blood sample
radioactivity measurements and by autoradiography of plasma samples
following resolution by gel electrophoresis. Factor V disappeared with a
half-life (t1/2) of 12.98 +/- 1.85 hours and was cleared without obvious
degradation of the molecule during circulation. The radioactivity
associated with the thrombin activated FV mixture, which consisted of the
Mr = 220,000 activation intermediate, the Mr = 150,000 activation peptide,
the heavy chain (HC) and the light chain (LC) of FVa, was cleared in a
nonlinear manner. The HC and LC were removed with t1/2 < 20 minutes. The
apparent molecular weight (Mr) = 220,000 and Mr = 150,000 fragments were
cleared with t1/2 > 6 hours and t1/2 > 30 hours, respectively.
Volume 86,
Issue 7,
pp. 2616-2623,
10/01/1995
Copyright © 1995 by The American Society of Hematology
