Antibody-detectable changes in fibrinogen adsorption affecting platelet activation on polymer surfaces.
Reactivity of platelets with an artificial surface exposed to whole blood is correlated with the concentration of adsorbed fibrinogen detectable by antifibrinogen antibodies. To examine the effect on platelets of the organization (distribution, orientation, conformation) of fibrinogen adsorbed on a hydrophobic surface, we studied the binding of polyclonal and monoclonal antifibrinogen antibodies to polyalkyl methacrylate polymers previously exposed to purified fibrinogen solution or diluted plasma and compared the results with platelet retention in methacrylate bead columns. There was an increase in platelet retention following diluted plasma pretreatment, which was eliminated by a polyclonal antibody against fibrinogen or against a gamma-(395-411) peptide from fibrinogen and was reduced by monoclonal antibodies (4A5, 4-2) against other COOH-terminal gamma-chain epitopes. Monoclonal antibody 10E5 against the fibrinogen receptor GpIIb/IIIa totally inhibited platelet retention in the bead columns. Our data suggest that different methacrylate polymers induce different changes in adsorbed fibrinogen, which may interfere with its interaction with platelets, and that platelet retention in a methacrylate bead column involves interaction of the COOH-terminal end of the gamma-chain of adsorbed fibrinogen with platelet GpIIb/IIIa receptors.
Shiba
E
E
Beth Israel Hospital, Boston 02215.
Lindon
J N
JN
Kushner
L
L
Matsueda
G R
GR
Hawiger
J
J
Kloczewiak
M
M
Kudryk
B
B
Salzman
E W
EW
D000327:Adsorption; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D001792:Blood Platelets / Q000502:physiology; D005340:Fibrinogen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D066298:In Vitro Techniques; D007700:Kinetics; D008768:Methylmethacrylates; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D011109:Polymethacrylic Acids; D011485:Protein Binding
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D008768:Methylmethacrylates; D010980:Platelet Membrane Glycoproteins; D011109:Polymethacrylic Acids; D005340:Fibrinogen; C068872:polybutyl methacrylate