Autocrine amplification of integrin alpha IIb beta 3 activation and platelet adhesive responses by deoxyribose-1-phosphate

作者：Vara Dina S; Campanella Michelangelo; Canobbio Ilaria; Dunn Warwick B; Pizzorno Giuseppe; Hirano Michio; Pula Giordano^*

来源：Thrombosis and Haemostasis, 2013, 109(6): 1108-1119.

DOI：10.1160/TH12-10-0751

• Platelets
• reactive oxygen species
• deoxyribose-1-phosphate
• integrin
• redox signalling

Using direct injection mass spectrometry (DIMS) we discovered that deoxyribose-1-phosphate (dRP) is released by platelets upon activation. Interestingly, the addition of exogenous dRP to human platelets significantly increased platelet aggregation and integrin alpha IIb beta 3 activation in response to thrombin. In parallel, genetically modified platelets with double genetic deletion of thymidine phosphorylase and uridine phosphorylase were characterised by reduced release of dRP, impaired aggregation and decreased integrin alpha IIb beta 3 activation in response to thrombin. In vitro platelet adhesion onto fibrinogen and collagen under physiological flow conditions was potentiated by treatment of human platelets with exogenous dRP and impaired in transgenic platelets with reduced dRP release. Human and mouse platelets responded to dRP treatment with a sizeable increase in reactive oxygen species (ROS) generation and the pre-treament with the antioxidant apocynin abolished the effect of dRP on aggregation and integrin activation. Experiments directly assessing the activation of the small G protein Rap1b and protein kinase C suggested that dRP increases the basal levels of activity of these two pivotal platelet-activating pathways in a redox-dependent manner. Taken together, we present evidence that dRP is a novel autocrine amplifier of platelet activity, which acts on platelet redox levels and modulates integrin alpha IIb beta 3.

• 出版日期2013-6