Participation of α_IIbβ₃ in Platelet Microparticle Generation by Collagen plus Thrombin

Abstract

We investigated the role of α_IIbβ₃ in microparticle generation by normal and thrombasthenic platelets stimulated with collagen plus thrombin. Microparticle generation by normal platelets was scarcely inhibited by monoclonal antibodies for glyco-protein lb and glycoprotein IX. Although one monoclonal anti-α α_IIbβ₃ antibody (NNKY1-32) partly inhibited microparticle generation, 3 other monoclonal anti-α α_IIbβ₃ antibodies had little effect. However, the combination of 4 monoclonal anti- α_IIbβ₃ antibodies or treatment with a polyclonal anti- α_IIbβ₃ antibody significantly inhibited microparticle generation (p < 0.05). Microparticle generation by thrombasthenic platelets also occurred after stimulation with collagen plus thrombin, although at a significantly lower level compared with normal platelets. Monoclonal antibodies for resting α_IIbβ₃, P-selectin, activated α_IIbβ₃ and β₂-glycoprotein I bound to microparticles from healthy platelets. In contrast, only a monoclonal antibody for β₂-glycoprotein I bound to thrombasthenic microparticles. These results suggest that microparticle generation by collagen plus thrombin occurs via two different mechanisms which are dependent and independent of α_IIbβ₃, respectively. The α_IIbβ₃-dependent mechanism appears to require activation of α_IIbβ₃·

Effect of Ticlopidine on Platelet-Derived Microparticles in Patients with Connective Tissue Diseases

“…It has been found that platelets are hyperactivated under these pathological conditions [21]. Recently, much attention has been paid to PMP as a novel marker of platelet activation, in addition to the previously recognized CD62, CD63 and annexin V molecules [7]. We observed a significant elevation of PMP in patients with connective tissue diseases complaining of peripheral circulation disorders.…”

“…One of the responses of activated platelets to certain stimuli is the shedding of microparticles. Microparticles released from platelets (PMP) may play a role in the normal hemostatic response to vascular injury, since these particles exhibit prothrombinase activity [6,7]. On the other hand, it is also possible that local generation of PMP in small atherosclerotic arteries or arterioles may promote acute arterial occlusion by providing and expanding a catalytic surface for the coagulation cascade.…”

A biochemical study on the level of lipids and glycoproteins in the serum and platelets of liver cirrhotic bleeders.

“…Glycoproteins present in the platelet are highly important for the platelet adhesion and activation in response to blood vessel damage and crucial for normal hemostasis and these events are also thought to be primary in arterial thrombosis (Hiramatsu et al, 1976). Many receptors present in the platelets are glycoproteins and a wide variety of studies have been undertaken to confirm the mode of action of receptors (Nomura et al, 1996;Reverter et al, 1996). Platelet glycoprotein polymorphism has been intensively studied as a genetic risk factor.…”

Effect of Bezafibrate on Soluble Adhesion Molecules and Platelet Activation Markers in Patients With Connective Tissue Diseases and Secondary Hyperlipidemia

“…Ten microliters of I platelet suspension (3 x 1(TslmT.~ was added to 100 pLL of I Hepes-Tyrode buffer containing 5 nmol/L ethyleneglycoltetracetic acid (EGTA), and both intact and aggregated platelets were removed by centrifugation at 1000 g for 15 minutes to yield a supernatant containing microparticles only. Next, 10 Only cells and particles positive for GPIX were gated, to i distinguish platelets and microparticles from ~Tectrc~ni~ ; I noise. To differentiate between platelets and micropar-' I tidies, the lower limit of the platelet gate was set at the left border of the forward scatter profile of resting platelets.…”