Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice

PLoS One. 2014 Oct 14;9(10):e109409. doi: 10.1371/journal.pone.0109409. eCollection 2014.

Abstract

In platelets, group IVA cytosolic phospholipase A2 (cPLA2α) has been implicated as a key regulator in the hydrolysis of platelet membrane phospholipids, leading to pro-thrombotic thromboxane A2 and anti-thrombotic 12-(S)-hydroxyeicosatetranoic acid production. However, studies using cPLA2α-deficient mice have indicated that other PLA2(s) may also be involved in the hydrolysis of platelet glycerophospholipids. In this study, we found that group VIB Ca2+-independent PLA2 (iPLA2γ)-deficient platelets showed decreases in adenosine diphosphate (ADP)-dependent aggregation and ADP- or collagen-dependent thromboxane A2 production. Electrospray ionization mass spectrometry analysis of platelet phospholipids revealed that fatty acyl compositions of ethanolamine plasmalogen and phosphatidylglycerol were altered in platelets from iPLA2γ-null mice. Furthermore, mice lacking iPLA2γ displayed prolonged bleeding times and were protected against pulmonary thromboembolism. These results suggest that iPLA2γ is an additional, long-sought-after PLA2 that hydrolyzes platelet membranes and facilitates platelet aggregation in response to ADP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Animals
  • Blood Platelets / metabolism*
  • Calcium / metabolism
  • Collagen / metabolism
  • Disease Susceptibility
  • Group VI Phospholipases A2 / deficiency
  • Group VI Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phospholipids / analysis
  • Platelet Activation
  • Platelet Aggregation
  • Receptors, Purinergic P2Y / metabolism
  • Serotonin / metabolism
  • Signal Transduction
  • Spectrometry, Mass, Electrospray Ionization
  • Thrombosis / metabolism
  • Thrombosis / pathology
  • Thromboxane A2 / metabolism

Substances

  • Phospholipids
  • Receptors, Purinergic P2Y
  • Serotonin
  • Thromboxane A2
  • Adenosine Diphosphate
  • Collagen
  • Group VI Phospholipases A2
  • Calcium

Grant support

This work was in part by a Grant-in-Aid for Scientific Research (B) (21390036 and 25293033) and a Grant-in-Aid for Research Activity start-up (21890254) from the Japan Society for the Promotion of Science; by a Grant-in-Aid for Scientific Research on Innovative Areas (25116720) and a grant for Private University High Technology Research Center Project from the Ministry of Education, Sports, Science, Culture and Technology of Japan; and by a grant from the Terumo Life Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.