The bioactive phospholipid lysophosphatidic acid is released from activated platelets

TLDR

Lysophosphatidic acid is a water‑soluble phospholipid with hormone‑like and growth‑factor‑like activities that activates a G‑protein‑coupled receptor, yet its natural source remains unknown. Thrombin activation of platelets releases newly formed LPA into the extracellular space. Serum contains 1–5 µM albumin‑bound LPA, absent in platelet‑poor plasma, indicating platelet‑derived release during clotting and suggesting LPA may mediate inflammatory and proliferative responses to injury.

Abstract

Lysophosphatidic acid (LPA) is a water-soluble phospholipid with hormone-like and growth-factor-like activities. LPA activates a putative G-protein-coupled receptor in responsive cells, but the natural source of exogenous LPA is unknown. Here we show that LPA is present in mammalian serum in an active form (bound to albumin) at concentrations of 1-5 microM, but is not detectable in platelet-poor plasma, suggesting that LPA is produced during blood clotting. We find that thrombin activation of platelets prelabelled with [32P]Pi results in the rapid release of newly formed [32P]LPA into the extracellular environment. We conclude that LPA is a novel platelet-derived lipid mediator that may play a role in inflammatory and proliferative responses to injury.