The Clearance of Human Fibrinogen Fragments X and Y in Mice: A Process Mediated by the Fragment D Receptor

Summary

The clearance of radiolabeled human fibrinogen fragments X and Y was studied in the mouse model. Fragment X cleared rapidly from the circulation with less than 10% of the ligand remaining in the circulation at 4 hr. The clearance of fragment Y was somewhat slower, but was identical to the rate of clearance of fragment D,. Competition studies indicated that fragments X, Y, D, and D! dimer clear via the same, saturable pathway. Fragment E did not compete for the clearance of these ligands. Tissue distribution studies demonstrated that the liver was the principal site of clearance of all three ligands. The kidneys also cleared a fraction of each ligand in the order fragment D₃>D₂>D₁ >Y>X. This pattern suggests that renal clearance is a passive phenomenon dependent on the size of the fibrinogen degradation product.

Keywords

Fibrinogen fragments - Plasma clearance

• References

• 1 Gaffney PJ. The biochemistry of the degradation of fibrinogen and fibrin by plasmin. In Haemostasis and Thrombosis . Neri Semeri GG, Prentice CRM. (eds). pp 7-26 Academic Press; New York: 1979
• 2 Marder VJ, Shulman NR, Carroll WR. High molecular weight derivatives of human fibrinogen produced by plasmin. J Biol Chem 1969; 244: 2111-2119
• 3 Pizzo SV, Schwartz ML, Hill RL, McKee PA. The effect of plasmin on the subunit structure of human fibrinogen. J Biol Chem 1972; 247: 636-645
• 4 Doolittle RF. Fibrinogen and fibrin. In The Plasma Proteins . Putnam FW. (ed) pp 109-161 Academic Press; New York: 1975
• 5 Pizzo SV, Taylor LM, Schwartz ML, Hill RL, McKee PA. Subunit structure of fragment D from fibrinogen and fibrin fragments D. Thromb Res 1977; 10: 803-812
• 6 Haverkate F, Timan G. Protective effect of calcium in the plasmic degradation of fibrinogen and fibrinfragments D. Thromb Res 1977; 10: 803-812
• 7 Pizzo SV, Pasqua JJ. The Clearance of human fibrinogenfragments D₁, D₂, D₃, and fibrin fragment D₁ dimer in mice. Biochem Biophys Acta 1982; 718: 177-184
• 8 Pizzo SV, Schwartz ML, Hill RL, McKee PA. The effect of plasmin on the subunit structure of fibrin. J Biol Chem 1973; 248: 4574-4583
• 9 David GS, Reisfeld RA. Protein iodination with solid state lactoperoxidase. Biochemistry 1974; 13: 1014-1021
• 10 Gonias SL, Einarsson M, Pizzo SV. Catabolic pathways for streptokinase, plasmin and streptokinase activator complex in mice. J Clin Invest 1982; 70: 412-423
• 11 Imber MJ, Pizzo SV. Clearance and binding of two electrophoretic forms of human α₂-macroglobulin. J Biol Chem 1981; 256: 8134-8139