title: The role of fibrinogen A alpha chains in ADP-induced platelet aggregation in the presence of fibrinogen molecules containing gamma' chains.
abstract: Human plasma fibrinogen (Fgn) is heterogenous with respect to the size of its gamma chains, which differ in that residues 408 to 411 of gammaA chains (93% of total) are replaced in gamma' chains by a unique 20 amino acid sequence (gamma408 to gamma427). In this study, we compared the contribution to adenosine diphosphate (ADP)-induced platelet aggregation of the A alpha chains in Fgn molecules containing predominantly (fraction 1-2) or exclusively (peak 1 Fgn) gammaA chains with that of molecules containing approximately 50% gamma' chains (peak 2 Fgn). Using washed human platelets, we confirmed that the number of peak 2 Fgn molecules binding to platelets in the presence of ADP was about half the number of peak 1 Fgn molecules (18,962 +/- 2,298 v 44,366 +/- 16,096 molecules per platelet), and that isolated S-carboxymethylated (SCM) gammaA chains supported ADP-induced platelet aggregation nearly as well as peak 1 Fgn. In contrast, SCM-gamma' chains alone supported aggregation poorly, whereas a mixture of SCM-gammaA and gamma' chains (1:1 ratio) gave intermediate results. Despite the findings with isolated SCM-gamma' chains, we found that peak 2 Fgn supported platelet aggregation nearly as well as peak 1 Fgn. However, peak 2 Fgn from which carboxy (COOH)-terminal A alpha chain segments had been removed by digestion with plasmin showed a markedly decreased platelet aggregation potential. Peak 1 Fgn core fraction from an 88% to 90% coagulable plasmin digest, or Fgn fraction 1-9, which has a high gammaA/gamma' chain ratio (93:7), but lacks COOH-terminal regions of A alpha chains, supported platelet aggregation to the same extent as did intact peak 2 Fgn. These findings indicate that Fgn molecules containing gamma' chains can approach the aggregation potential of Fgn molecules containing predominantly or exclusively gammaA chains only if intact A alpha chains are also present.
authors.affiliation: Department of Medicine, University of Wisconsin Medical School, Milwaukee 53233.
authors.forename: D L
authors.initials: DL
authors.lastname: Amrani
authors.forename: P J
authors.initials: PJ
authors.lastname: Newman
authors.forename: D
authors.initials: D
authors.lastname: Meh
authors.forename: M W
authors.initials: MW
authors.lastname: Mosesson
mesh_terms: D000244:Adenosine Diphosphate; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000302:isolation & purification / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000032:analysis; D018000:Receptors, Peptide
chemical_list: D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C048650:fibrin-fibrinogen degradation products receptor; D000244:Adenosine Diphosphate; D005340:Fibrinogen