Does the conformation of adsorbed fibrinogen dictate platelet interactions with artificial surfaces?
Platelet activation by polymer surfaces is thought to require preliminary adsorption of fibrinogen and perhaps changes in fibrinogen conformation. We measured fibrinogen adsorption by a series of polymers by two methods, using either 125I-labeled fibrinogen or 125I-labeled antifibrinogen antibodies, and correlated the results with platelet reactivity (retention and secretion) in columns of beads coated with the polymers. For polyalkyl methacrylates with 1 to 4 carbon side chains, platelet reactivity varied directly with increasing length of the alkyl side chain and with the quantity of bound fibrinogen recognizable by antifibrinogen antibody but not with the total quantity of fibrinogen adsorbed. The same pattern of results was seen with five antibody preparations, including affinity-purified Fab fragments against the D or E domain of fibrinogen. Tests of platelet retention and fibrinogen binding to four polyalkyl acrylates and to three unrelated polymers (polystyrene, polymethyl methacrylate, and a polyether polyurethane) indicated that platelet retention correlated positively with both total fibrinogen binding and with the amount of antibody-recognizable fibrinogen bound. Drugs that block platelet aggregation, but not adhesion, did not alter the hierarchy of platelet retention to the polyalkyl methacrylates. These data suggest that, contrary to previous views, platelet adhesion to artificial surfaces increases with increasing surface coverage of adsorbed fibrinogen if the bound fibrinogen maintains a conformation such that its functional domains remain recognizable by antibody probes.
D000327:Adsorption; D000906:Antibodies; D000954:Antigens, Surface / Q000276:immunology; D001792:Blood Platelets / Q000502:physiology*; D005340:Fibrinogen / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D010974:Platelet Aggregation / Q000187:drug effects; D011108:Polymers
D000906:Antibodies; D000954:Antigens, Surface; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011108:Polymers; D005340:Fibrinogen