Clearance of human fibrin and fibrinogen degradation products in mice and their interference with the human platelet-fibrinogen interaction

Thesis/Dissertation · Sat Jan 01 04:00:00 EST 1983

OSTI ID:5959246

Pasqua, J J

Binding studies using radioiodinated human fibrinogen and fibrinoge and fibrin degradation products were performed with washed human platelets in order to determine the domain of the fibrinogen molecule responsible for binding to the platelet receptor. The studies suggested that the degradation products interfered with fibrinogen binding by interacting with the fibrinogen molecule, not the platelet receptor. Two methods were developed to test this hypothesis. The first technique utilized molecular exclusion with Sephacryl S-200. The second method measured the affinity of the fragments for fibrinogen-Sepharose. These studies supported the inference drawn from the platelet binding studies and revealed that fibrinogen interacts with fragments D and E. The clearance of radioiodinated human fibrinogen fragments D/sub 1/, D/sub 2/, and D/sub 3/ and fibrin fragment D/sub 1/ dimer were studied in female CD-1 mice. Competition studies demonstrated that the clearance was mediated through a specific, noncarbohydrate dependent receptor. Autopsies showed that the fragments cleared primarily in liver and kidney while light microscopic autoradiography revealed that 80% of the liver uptake was in hepatocytes. These studies were extended to include the earlier intermediate fibrinogen degradation products fragments X and Y. Fragment X cleared very rapidly and fragment Y cleaved at a rate identical to that of fragment D/sub 1/. Competition studies demonstrated that fragments X, Y, and D/sub 1/ and D/sub 1/ dimer clear via the same saturable pathway.

• Research Organization: Duke Univ., Durham, NC (USA)
• OSTI ID: 5959246
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
AUTORADIOGRAPHY
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BLOOD-PLASMA CLEARANCE
BODY
BODY FLUIDS
CHEMICAL BONDS
CHEMISTRY
CLEARANCE
COAGULANTS
DIGESTIVE SYSTEM
DRUGS
FIBRIN
FIBRINOGEN
GLANDS
GLOBULINS
HEMATOLOGIC AGENTS
HEMOSTATICS
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
LIVER
MAMMALS
MAN
MATERIALS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RECEPTORS
SCLEROPROTEINS
TRACER TECHNIQUES
VERTEBRATES