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

Biochem Biophys Res Commun. 2021 Sep 10:569:86-92. doi: 10.1016/j.bbrc.2021.06.090. Epub 2021 Jul 5.

Abstract

Neutrophils undergo spontaneous apoptosis within 24-48 h after leaving bone marrow. Apoptotic neutrophils are subsequently phagocytosed and cleared by macrophages, thereby maintaining neutrophil homeostasis. Previous studies have demonstrated involvement of lysophosphatidylglucoside (lysoPtdGlc), a degradation product of PtdGlc, in modality-specific repulsive guidance of spinal sensory axons, via its specific receptor GPR55. In the present study, using human monocytic cell line THP-1 as a model, we demonstrated that lysoPtdGlc induces monocyte/macrophage migration with typical bell-haped curve and a peak at concentration 10-9 M. Lysophosphatidylinositol (lysoPtdIns), a known GPR55 ligand, induced migration at higher concentration (10-7 M). LysoPtdGlc-treated cells had a polarized shape, whereas lysoPtdIns-treated cells had a spherical shape. In EZ-TAXIScan (chemotaxis) assay, lysoPtdGlc induced chemotactic migration activity of THP-1 cells, while lysoPtdIns induced random migration activity. GPR55 antagonist ML193 inhibited lysoPtdGlc-induced THP-1 cell migration, whereas lysoPtdIns-induced migration was inhibited by CB2-receptor inverse agonist. SiRNA experiments showed that GPR55 mediated lysoPtdGlc-induced migration, while lysoPtdIns-induced migration was mediated by CB2 receptor. Our findings, taken together, suggest that lysoPtdGlc functions as a chemotactic molecule for human monocytes/macrophages via GPR55 receptor, while lysoPtdIns induces random migration activity via CB2 receptor.

Keywords: Chemotactic factor; GPR55; Human macrophages; Human monocytes; Lysophosphatidylglucoside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Chemotaxis / drug effects
  • Chemotaxis / physiology
  • Glucosides / chemistry
  • Glucosides / pharmacology*
  • Humans
  • Lysophospholipids / chemistry*
  • Lysophospholipids / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • RNA Interference
  • Receptors, Cannabinoid / genetics
  • Receptors, Cannabinoid / metabolism*
  • THP-1 Cells

Substances

  • GPR55 protein, human
  • Glucosides
  • Lysophospholipids
  • Receptors, Cannabinoid
  • lysophosphatidylinositol