|
|
 Previous Article | Table of Contents | Next Article 
Kinetic characterization of a saturable pathway for rapid clearance of
circulating fibrin monomer
BN Dardik and JR Shainoff
The mechanism of clearance of circulating fibrin monomer was investigated
in rabbits through (1) study of decay in plasma concentrations of
125I-labeled monomers with variant fibrinopeptide content and (2)
concurrent analysis of decay of the monomers relative to coinjected
131I-fibrinogen. Under the conditions employed, essentially all of the
fibrin became distributed in a soluble form in plasma and decayed
independently of the coinjected fibrinogen. Among the species of fibrin
studied, monomer lacking fibrinopeptide A alone (alpha-fibrin) underwent
very rapid clearance by a saturable mechanism that was not evident in
relatively sluggish clearance of monomer lacking either fibrinopeptide B
alone (beta-fibrin) or both fibrinopeptides A and B (alpha beta-fibrin).
Decay of alpha-fibrin conformed with a kinetic mechanism involving
first-order permeation of the fibrin into extravascular space at a rate
equivalent to that of permeation of fibrinogen; unlike fibrinogen, however,
the alpha-fibrin underwent immediate absorption in parallel with permeation
(t1/2 = 2.6 hours) at doses below an apparent saturating level of 3 mg/kg.
At doses near the absorptive limit, the uptake accompanying permeation
diminished as in a second-order kinetic mechanism, and at very high doses
the plasma decay of the alpha-fibrin approached that of fibrinogen. The
beta- and alpha beta-fibrins also permeated extravascular space in parallel
with fibrinogen, but absorption proceeded sluggishly (t1/2 = 11 and 16
hours, respectively) at low doses and did not change with increasing dose.
The uniquely rapid and saturable clearance of alpha-fibrin is suggested to
involve uptake through the fibrin aggregation site that is blocked by
fibrinopeptide A in fibrinogen and beta-fibrin and by tight binding to
fibrinogen in soluble complexes formed by alpha beta-fibrin. A corollary of
this hypothesis is that rapid uptake depends on dissociability of fibrin
complexes for access to the aggregation site, a mechanism that is just the
converse of uptake through aggregation.
Volume 65,
Issue 3,
pp. 680-688,
03/01/1985
Copyright © 1985 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Kerlin, B. C. Cooley, B. H. Isermann, I. Hernandez, R. Sood, M. Zogg, S. B. Hendrickson, M. W. Mosesson, S. Lord, and H. Weiler
Cause-effect relation between hyperfibrinogenemia and vascular disease
Blood,
March 1, 2004;
103(5):
1728 - 1734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Shainoff, G. B. Smejkal, P. M. DiBello, O. V. Mitkevich, P. J. Levy, C. E. Dempfle, and H. Lill
Isolation and Characterization of the Fibrin Intermediate Arising from Cleavage of One Fibrinopeptide A from Fibrinogen
J. Biol. Chem.,
September 27, 1996;
271(39):
24129 - 24137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
