Platelet surfaces

A number of promising approaches have emerged in the eady to mid-1980s that may ultimately provide an agent. In general these approaches have focused on compounds that bind to the platelet glycoprotein (GP) Ilb/Ilia receptor. This receptor on the platelet surface is responsible for its binding to... 

GP 2[ [R 3a[The sputtered silver on aluminum alloy (AlMg3) platelets, machined by thin-wire pEDM, were smooth and dense. On prolonged operation under reaction conditions, small silver particles are generated by surface diffusion so that also the blank aluminum platelet surface is exposed (20 vol.-% ethylene, 80 vol.-% oxygen 3 bar 0.23-2 s 250 °C) [43]. 

CD62P or P-selectin, which is a component of the platelet a granule membrane of resting platelets. It is expressed on the platelet surface membrane only after a granule secretion. P-selectin mediates the adhesion of activated platelets to neutrophils and monocytes. 

Of the four markers just mentioned, the expression of P-selectin on the activated platelets is the most widely studied. However, CD62P may not be the ideal marker for detection of circulating degranulated platelets, because they may rapidly lose their surface P-selectin but yet may continue to function. The decrease in the platelet surface expression of the GPIb-IX-V complex (CD42) perhaps represents a more sensitive marker of in vivo platelet activation. Apparently platelet activation related to strenuous exercise is more readily detected using CD42 than other markers (99). 

ReoPro (Abciximab, Fab fragments derived from a chimaeric Mab, directed against the platelet surface receptor GPIIb/IIIa)... 

CysNO is a potent anti-platelet agent Like other nitrosothiols, it increased the intracellular GMP level in platelets in vitro and inhibited collagen-induced platelet aggregation and ADP-induced activation of GP Ilb/IIIa on the platelet surface [45, 47]. However its potency to release NO, stimulate platelet soluble GS and elevate intracellular platelet cGMP was higher than of GSNO [47, 72]. 

SNAC is the most potent inhibitor of collagen-induced platelet aggregation in vitro compared to other S-nitrosothiols (SNAP, GSNO, CysNO and HomocysNo). Although it increased cGMP-levels in platelets [47], SNAC only partially inhibited thrombin-induced P-selectin expression on a platelet surface [79]. 

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

Kieffer, N., Guichard, J., and Breton-Gorius, J., Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. Am. J. Pathol. 140, 57-73... 

Ouimet, H., Freeman, J. E., and Loscalzo, J., Kinetics and mechanism of platelet surface plasminogen activity by tissue plasminogen activator. Biochem. 33, 2970-2976 (1994). 

A remarkably potent compound, its effects on platelets are observed at concentrations of 10 11 to 10 10 M. Both lyso-PAF and the glycero-1- phosphocho-line enantiomer are inactive. Specific receptors for this factor are evidently present on platelet surfaces.6-8... 

Ca2+ which helps to tie these proteins to the phospholipids of platelet surfaces. In factors VII, IX, X, and protein C this Ca2+-binding domain is followed by two epidermal growth factor (EGF)-like domains, each containing one residue of en/Firo-P-hydroxyaspartate or hydroxyasparagine formed by hydroxylation of an aspartate or asparagine residue in the first EGF-like domain.540,540a,b The C-terminal catalytic domain of each enzyme contains the protease active site. 

The platelet surface contains aggregin, a membrane protein with a molecular weight of 100 kDa, which has physical and immunochemical properties that differ from those of platelet glycoprotein Ilia. 

Platelet activation leads to the formation of platelet-derived microparticles derived from the platelet surface. These microvesicles typically account for 25% to 30% of platelet procoagulant activity and factor V binding sites (34,39),... 

Bevers EM, Rosing J, Zwaal RFA. Development of procoagulant binding sites on the platelet surface. In WestweekJ, Scully MF McIntyre DE, KakkarVV eds. Mechanisms of Stimulus Response Coupling in Platelets, New York Plenum Press, 1985 359-372. 

---