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Reduced platelet adhesion in flowing blood to fibrinogen by alterations in segment γ316–322, part of the fibrin‐specific region *
Author(s) -
Remijn Jasper A.,
IJsseldijk Martin J. W.,
Van Hemel Bettien M.,
Galanakis Dennis K.,
Hogan Kelly A.,
Lounes Karim C.,
Lord Susan T.,
Sixma Jan J.,
De Groot Philip G.
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03467.x
Subject(s) - fibrinogen , fibrin , platelet , chemistry , adhesion , platelet adhesiveness , recombinant dna , biochemistry , biophysics , microbiology and biotechnology , immunology , medicine , platelet aggregation , biology , gene , organic chemistry
Summary. The interaction of platelets with fibrinogen is a key event in the maintenance of a haemostatic response. It has been shown that the 12‐carboxy‐terminal residues of the γ‐chain of fibrinogen mediate platelet adhesion to immobilized fibrinogen. These studies, however, did not exclude the possibility that other domains of fibrinogen are involved in interactions with platelets. To obtain more insight into the involvement of other domains of fibrinogen in platelet adhesion, we studied platelet adhesion in flowing blood to patient dysfibrinogen Vlissingen/Frankfurt IV (V/FIV), to several variant recombinant fibrinogens with abnormalities in the γ‐chain segments γ318–320 and γ408–411. Perfusion studies at physiological shear rates showed that platelet adhesion was absent to γΔ408‐411, slightly reduced to the heterozygous patient dysfibrinogen V/FIV and strongly reduced to the homozygous recombinant fibrinogens: γΔ319‐320, γ318Asp→Ala and γ320Asp→Ala. Furthermore, antibodies raised against the sequences γ308–322 and γ316–333 inhibited platelet adhesion under shear conditions. These experiments indicated that the overlapping segment γ316–322 contains amino acids that could be involved in platelet adhesion to immobilized fibrinogen under flow conditions. In soluble fibrinogen, this sequence is buried inside the fibrinogen molecule and becomes exposed after polymerization. In addition, we have shown that this fibrin‐specific sequence also becomes exposed when fibrinogen is immobilized on a surface.