Involvement of the alpha chain in fibrin clot formation. Effect of monoclonal antibodies.
Murine monoclonal antibodies 9C3, 7B1, and 9E9 have been obtained using native human fibrinogen as the antigen. The antibodies reacted with the epitopes in the COOH-terminal domain of the A alpha chain. Fragmentation of the A alpha chain with plasmin, and, as in the case of the 9E9 epitope, with V8 protease, followed by isolation of the smallest reacting peptides, allowed the localization of the epitopes for 9C3, 7B1, and 9E9 to the amino acid sequences of alpha 240-268, alpha 425-440, and alpha 541-574, respectively. All three monoclonal antibodies strongly inhibited the rate of fibrin polymer assembly from monomers, both in the purified system and in the human plasma. The mechanism of this strong inhibition implied a rapid formation of fibrin protofibrils, followed by capping with IgG molecules of protofibrils containing approximately ten monomers. These observations demonstrated that certain regions in the COOH terminus of the alpha chain may play an important role in the assembly of a fibrin clot, presumably being involved in lateral aggregation of protofibrils.
Cierniewski
C S
CS
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Budzynski
A Z
AZ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001777:Blood Coagulation; D000939:Epitopes; D005337:Fibrin / Q000737:chemistry / Q000502:physiology*; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D012995:Solubility
D000911:Antibodies, Monoclonal; D000939:Epitopes; D010455:Peptides; D005337:Fibrin; D005340:Fibrinogen