Tirofiban potentiates agonist-induced platelet activation and degranulation, despite effectively inhibiting aggregation

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Název: Tirofiban potentiates agonist-induced platelet activation and degranulation, despite effectively inhibiting aggregation
Autoři: Martina Aguiar Bucsai, Christian Idel, Barbara Wollenberg, Christine Mannhalter, Admar Verschoor
Zdroj: Platelets, Vol 33, Iss 8, Pp 1192-1198 (2022)
Informace o vydavateli: Informa UK Limited, 2022.
Rok vydání: 2022
Témata: Blood Platelets, tirofiban, Platelet Aggregation, Platelet Glycoprotein GPIIb-IIIa Complex, Platelet Activation, platelet inhibition, P-Selectin, 03 medical and health sciences, 0302 clinical medicine, Tirofiban, platelet aggregation, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, platelet activation, Humans, Tyrosine, Diseases of the blood and blood-forming organs, Receptors, Thrombin, RC633-647.5, Chemokine CCL5, platelet degranulation, Platelet Aggregation Inhibitors
Popis: We aimed to investigate the effects of integrin αIIbβ3 inhibitor tirofiban on hallmarks of platelet activation, degranulation, and aggregation during its use to analyze activated but non-complexed platelets via flow cytometry. To do so, we used washed platelets from healthy human donors. We combined aggregometry, an assay of platelet functionality, with flow cytometry and ELISA to detect and correlate, respectively, platelet aggregation, activation, and granule release. While tirofiban effectively inhibited agonist-induced platelet aggregation (thrombin receptor-activating peptide 6 (TRAP), convulxin (CVX), U46619 and IV.3), the surface expression of P-selectin and CD63 and granule release of RANTES were significantly increased, indicating that tirofiban enhances degranulation, uncoupled from aggregation. The results show that tirofiban alters the activation phenotype of platelets, something that should be considered when using tirofiban to enable flow cytometric analysis of activated but unaggregated platelet suspensions.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1369-1635
0953-7104
DOI: 10.1080/09537104.2022.2078489
DOI: 10.6084/m9.figshare.20070108
DOI: 10.6084/m9.figshare.20070108.v1
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/35701857
https://doaj.org/article/67d154783c2d4217a594f18f8ee8fe79
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....9e80b286893e1f4297f2433fe55838fe
Databáze: OpenAIRE
Popis
Abstrakt:We aimed to investigate the effects of integrin αIIbβ3 inhibitor tirofiban on hallmarks of platelet activation, degranulation, and aggregation during its use to analyze activated but non-complexed platelets via flow cytometry. To do so, we used washed platelets from healthy human donors. We combined aggregometry, an assay of platelet functionality, with flow cytometry and ELISA to detect and correlate, respectively, platelet aggregation, activation, and granule release. While tirofiban effectively inhibited agonist-induced platelet aggregation (thrombin receptor-activating peptide 6 (TRAP), convulxin (CVX), U46619 and IV.3), the surface expression of P-selectin and CD63 and granule release of RANTES were significantly increased, indicating that tirofiban enhances degranulation, uncoupled from aggregation. The results show that tirofiban alters the activation phenotype of platelets, something that should be considered when using tirofiban to enable flow cytometric analysis of activated but unaggregated platelet suspensions.
ISSN:13691635
09537104
DOI:10.1080/09537104.2022.2078489