Streptokinase-induced platelet activation involves antistreptokinase antibodies and cleavage of protease-activated receptor-1

Citation
Jp. Mcredmond et al., Streptokinase-induced platelet activation involves antistreptokinase antibodies and cleavage of protease-activated receptor-1, BLOOD, 95(4), 2000, pp. 1301-1308
Citations number
41
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
95
Issue
4
Year of publication
2000
Pages
1301 - 1308
Database
ISI
SICI code
0006-4971(20000215)95:4<1301:SPAIAA>2.0.ZU;2-9
Abstract
Streptokinase activates platelets, limiting its effectiveness as a thrombol ytic agent. The role of antistreptokinase antibodies and proteases in strep tokinase-induced platelet activation was investigated. Streptokinase induce d localization of human IgG to the platelet surface, platelet aggregation, and thromboxane A(2) production. These effects were inhibited by a monoclon al antibody to the platelet Pc receptor, IV.3. The platelet response to str eptokinase was also blocked by an antibody directed against the cleavage si te of the platelet thrombin receptor, protease-activated receptor-1 (PAR-1) , but not by hirudin or an active site thrombin inhibitor, Ro46-6240, In pl asma depleted of plasminogen, exogenous wild-type plasminogen, but not an i nactive mutant protein, S(741)A plasminogen, supported platelet aggregation , suggesting that the protease cleaving PAR-1 was streptokinase-plasminogen , Streptokinase-plasminogen cleaved a synthetic peptide corresponding to PA R-1, resulting in generation of PAR-1 tethered ligand sequence and selectiv ely reduced binding of a cleavage-sensitive PAR-1 antibody in intact cells. A combination of streptokinase, plasminogen, and antistreptokinase antibod ies activated human erythroleukemic cells and was inhibited by pretreatment with IV.3 or pretreating the cells with the PAR-I agonist SFLLRN, suggesti ng Pc receptor and PAR-1 interactions are necessary for cell activation in this system also, Streptokinase-induced platelet activation is dependent on both antistreptokinase-fc receptor interactions and cleavage of PAR-1, (C) 2000 by The American Society of Hematology.