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Lysophosphatidylglucoside is a GPR55 -mediated chemotactic molecule for human monocytes and macrophages

Xiaojia Li1, Kei Hanafusa1, Madoka Kage1

  • 1Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba 279-0021, Japan.

Biochemical and Biophysical Research Communications
|July 8, 2021
PubMed

Insights

Lysophosphatidylglucoside (lysoPtdGlc) acts as a chemotactic signal, guiding monocytes and macrophages via the GPR55 receptor. Lysophosphatidylinositol (lysoPtdIns) induces random migration through the CB2 receptor.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Neutrophil homeostasis relies on macrophage phagocytosis of apoptotic neutrophils.
  • Lysophosphatidylglucoside (lysoPtdGlc), a phosphatidylglucoside (PtdGlc) metabolite, is known to guide spinal sensory axons via GPR55.
  • The role of lysoPtdGlc in immune cell migration is not well understood.

Purpose of the Study:

  • To investigate the role of lysoPtdGlc and lysophosphatidylinositol (lysoPtdIns) in monocyte/macrophage migration.
  • To elucidate the specific receptors and signaling pathways involved in lysoPtdGlc and lysoPtdIns-mediated cell migration.

Main Methods:

  • Utilized the human monocytic cell line THP-1 as a model system.
  • Performed chemotaxis assays (EZ-TAXIScan) to assess cell migration in response to lysoPtdGlc and lysoPtdIns.
  • Employed GPR55 and CB2 receptor antagonists/agonists and siRNA to investigate receptor-mediated signaling.

Main Results:

  • LysoPtdGlc induced chemotactic migration of THP-1 cells, with optimal activity at 10-9 M, and promoted cell polarization.
  • LysoPtdIns induced random migration of THP-1 cells at 10-7 M, resulting in a spherical cell shape.
  • GPR55 antagonist ML193 blocked lysoPtdGlc-induced migration, while CB2 inverse agonist inhibited lysoPtdIns-induced migration.
  • siRNA experiments confirmed GPR55 mediation for lysoPtdGlc and CB2 receptor mediation for lysoPtdIns.

Conclusions:

  • LysoPtdGlc functions as a chemotactic molecule for human monocytes/macrophages, signaling through the GPR55 receptor.
  • LysoPtdIns induces random migration of monocytes/macrophages via the CB2 receptor.
  • These findings highlight distinct roles for lysoPtdGlc and lysoPtdIns in regulating immune cell movement and homeostasis.
Keywords:
Chemotactic factorGPR55Human macrophagesHuman monocytesLysophosphatidylglucoside

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