title: Dynamics of GPIIb/IIIa-mediated platelet-platelet interactions in platelet adhesion/thrombus formation on collagen in vitro as revealed by videomicroscopy.
abstract: The conventional description of platelet interactions with collagen-coated surfaces in vitro, based on serial static measurements, is that platelets first adhere and spread to form a monolayer and then recruit additional layers of platelets. To obtain dynamic information, we studied gravity-driven platelet deposition in vitro on purified type 1 collagen by video phase-contrast microscopy at 22 degrees C. With untreated human and wild-type mouse platelets, soon after the initial adhesion of a small number of "vanguard" platelets, "follower" platelets attached to the spread-out vanguard platelets. Follower platelets then adhered to and spread onto nearby collagen or over the vanguard platelets. Thus, thrombi formed as a concerted process rather than as sequential processes. Treatment of human platelets with monoclonal antibody (mAb) 7E3 (anti-GPIIb/IIIa (alphaIIbbeta3) + alphaVbeta3) or tirofiban (anti-GPIIb/IIIa) did not prevent platelet adhesion but nearly eliminated the deposition of follower platelets onto vanguard platelets and platelet thrombi. Similar results were obtained with Glanzmann thrombasthenia platelets. Wild-type mouse platelets in the presence of mAb 1B5 (anti-GPIIb/IIIa) and platelets from beta3-null mice behaved like human platelets in the presence of 7E3 or tirofiban. Deposition patterns of untreated human and wild-type mouse platelets were consistent with random distributions under a Poisson model, but those obtained with 7E3- and tirofiban-treated human platelets, 1B5-treated mouse platelets, or beta3-null platelets demonstrated a more uniform deposition than predicted. Thus, in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation and alters the pattern of platelet deposition.
authors.affiliation: Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Dipti
authors.initials: D
authors.lastname: Patel
authors.forename: Heikki
authors.initials: H
authors.lastname: Väänänen
authors.forename: Markéta
authors.initials: M
authors.lastname: Jirousková
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Carol
authors.initials: C
authors.lastname: Bodian
authors.forename: Barry S
authors.initials: BS
authors.lastname: Coller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D018715:Microscopy, Video; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology / Q000502:physiology*; D013915:Thrombasthenia / Q000097:blood; D013927:Thrombosis / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D019039:Platelet Glycoprotein GPIIb-IIIa Complex