Profiling oxylipins released from human platelets activated through the GPVI collagen receptor

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.' 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 TxA(2) and PGD/E-2, but also significantly inhibited the release of 11-HETE (89 +/- 3%) and 9-HODE (74 +/- 6%), and reduced 15-HETE and 13-HODE by similar to 33 %. Inhibition of 12-LOX by either esculetin or ML355 inhibited the release of all oxylipins apart from 15-HETE. These findings suggest mutes to modify the production of bioactive molecules released by activated platelets.

Automated summary

In addition to haemostasis, platelets play a role in various pathological processes through the release of bioactive molecules upon activation. This study found that platelets stimulated by GPVI release multiple oxylipins with biological properties. Inhibition of COX-1 and 12-LOX could modify the production of these bioactive molecules released by activated platelets.