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  • Title: Profiling oxylipins released from human platelets activated through the GPVI collagen receptor.
    Author: Turnbull RE, Sander KN, Turnbull J, Barrett DA, Goodall AH.
    Journal: Prostaglandins Other Lipid Mediat; 2022 Feb; 158():106607. PubMed ID: 34942378.
    Abstract:
    In addition to haemostasis, platelets are involved in pathological processes, often driven by material released upon activation. Interaction between collagen and glycoprotein VI (GPVI) is a primary platelet stimulus that liberates arachidonic acid and linoleic acid from membrane phospholipids. These are oxidised by cyclooxygenase-1 (COX-1) and 12-lipoxygenase (12-LOX) to eicosanoids and other oxylipins with various biological properties. Using liquid chromatography-tandem mass spectrometry we found that GPVI-stimulated platelets released significant levels of ten oxylipins; the well documented TxA2 and 12-HETE, PGD2 and PGE2, as well as 8-, 9-, 11-, and 15-HETE, 9- and 13-HODE.1 Levels of oxylipins released from washed platelets mirrored those from platelets stimulated in the presence of plasma, indicating generation from intracellular, rather than exogenous AA/LA. Inhibition of COX-1 with aspirin, as expected, completely abolished production of TxA2 and PGD/E2, but also significantly inhibited the release of 11-HETE (89 ± 3%) and 9-HODE (74 ± 6%), and reduced 15-HETE and 13-HODE by ∼33 %. Inhibition of 12-LOX by either esculetin or ML355 inhibited the release of all oxylipins apart from 15-HETE. These findings suggest routes to modify the production of bioactive molecules released by activated platelets.
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