Substances that polymerize or depolymerize cytoskeletal proteins affect platelet spreading and thrombus-formation on surfaces coated with human collagen isotypes I, IV, and V.
The effect of substances that affect platelet cytoskeleton on the interaction of gel-filtered platelets with surfaces coated with human monomeric type I, IV, and V collagen was studied. The sulfhydryl group oxidizing agent azodicarboxylic acid-bis-dimethylamide (diamide) which causes disulfide-linked polymer formation of certain cytoskeletal proteins, the actin-polymerization inhibitor, cytochalasin B, and 2-mercaptopropionylglycine (2-MPG), a cell-permeable SH-reagent, completely abolish adhesion-induced platelet spreading and mural platelet aggregate formation on collagen-coated surfaces. Extrusion of pseudopods was inhibited by cytochalasin B and 2-MPG as well as by diamide, but only the latter caused spherulation of platelets, whereas cytochalasin B and 2-MPG left the discoid shape of resting platelets intact. These effects are dose-dependent and are not accounted for by a chemical modification of the collagenous substrates by the cytoskeletal perturbing substances. The present data indicate that (i) cytoskeletal rearrangements are essential in adhesion-induced platelet spreading and aggregate formation on surfaces coated with collagen, but not in supporting the initial attachment of native platelets to the substrate; (ii) both, polymerization and depolymerization of actin filaments affect platelet activation; (iii) the sulfhydryl-disulfide status of the platelet seems to be a possible target for anti-platelet drugs, since chemical modification of platelets by the GSH-GSSG-active substances, diamide and 2-MPG, leads to a reversible inhibition of adhesion-induced platelet activation.
Misselwitz
F
F
Central Institute for Cardiovascular Research, Academy of Sciences, Berlin-Buch, GDR.
Domogatsky
S P
SP
Repin
V S
VS
Spangenberg
P
P
Till
U
U
D002850:Chromatography, Gel; D003094:Collagen / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011108:Polymers; D008625:Tiopronin / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D003571:Cytochalasin B; D003094:Collagen; D008625:Tiopronin