alpha IIb beta 3 redistribution triggered by receptor cross-linking.
Fibrinogen binding to alpha IIb beta 3 on adherent, spread platelets triggers active, cytoskeletally-directed redistribution of fibrinogen/alpha IIb beta 3 complexes on the platelet surface. Gold-conjugated fibrinogen, unlabeled, soluble fibrinogen, and individual fibrinogen molecules have been demonstrated to trigger receptor redistribution. Here we examine the respective roles of receptor cross-linking and ligand occupancy of receptors in initiating this movement. Monovalent, alpha IIb beta 3-binding fibrinogen fragments RGDS and HHLGGAKQAGDV did not trigger receptor redistribution, suggesting that ligand binding to a single receptor is an insufficient stimulus. Binding of monoclonal antibodies 10E5, AP2, and AP3 to the receptor did not trigger receptor movement. However, cross-linking these receptor-bound monoclonal antibodies by polyclonal anti-mouse IgG or by conjugation of the anti-receptor antibody to large colloidal gold particles triggered receptor redistribution identical in rate, pattern, and final distribution to that previously seen with fibrinogen binding. We conclude that receptor cross-linking provides the signal for initiation of fibrinogen/alpha IIb beta 3 complex redistribution on platelet surfaces.
Simmons
S R
SR
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison 53706, USA.
Sims
P A
PA
Albrecht
R M
RM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry / Q000494:pharmacology*; D017979:Gold Colloid / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008024:Ligands; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology / Q000378:metabolism*; D011940:Receptor Aggregation / Q000187:drug effects*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D017979:Gold Colloid; D007074:Immunoglobulin G; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005340:Fibrinogen; C049554:glycyl-arginyl-glycyl-aspartyl-serine; C046617:arginyl-glycyl-aspartyl-serine