Platelet aggregation was induced by collagen or ADP and epinephrine. Integrin αIIbx3b2;3-fibrinogen binding was evaluated on prostaglandins E1 (PGE1)-treated washed platelets or baby hamster kidney (BHK) cells expressing human αIIbx3b2;3. Integrin was directly activated by an anti-ligand induced binding site (LIBS) PT25-2 antibody. The effect of sulfhydryl-reactive agents, such as allicin, glutathione, dithiobis nitrobenzoic acid (DTNB) and disulfiram, was tested on αIIbx3b2;3 activity.
Allicin (40 µM) completely inhibited washed platelets agonist-induced aggregation. Both allicin and disulfiram (40 µM) inhibited αIIbx3b2;3-fibrinogen binding and P-selectin expression in washed platelets. However, there was an increase in αIIbx3b2;3-fibrinogen binding but not P-selectin expression in PGE1-treated washed platelets activated by PT25-2 antibody. At a high concentration (400 µM) both inhibited αIIbx3b2;3-fibrinogen binding. Similarly, in BHK cells expressing αIIbx3b2;3 activated by PT25-2 antibody, allicin at a low concentration increased αIIbx3b2;3 activity.
Allicin and disulfiram inhibit agonist-induced washed platelet activation probably via inhibition of platelet signaling, but enhance PT25-2 antibody-induced αIIbx3b2;3 integrin activity most likely by preventing reformation of disulfide bridges thereby stabilizing the active conformation of the integrin.