1. Lysophosphatidylglucoside is a GPR55 -mediated chemotactic molecule for human monocytes and macrophages
- Author
-
Hideoki Ogawa, Yasuko Nagatsuka, Madoka Kage, Tomomi Hotta, Yoshio Hirabayashi, Kenji Takamori, Kazuhisa Iwabuchi, Hitoshi Nakayama, Kei Hanafusa, Koki Kano, Ichiro Matsuo, Eriko Oshima, Noriko Yokoyama, and Xiaojia Li
- Subjects
THP-1 Cells ,Blotting, Western ,Biophysics ,Biochemistry ,Monocytes ,chemistry.chemical_compound ,Glucosides ,Cell Movement ,medicine ,Cannabinoid receptor type 2 ,Humans ,Inverse agonist ,Macrophage ,Receptors, Cannabinoid ,Receptor ,Neutrophil homeostasis ,Molecular Biology ,Chemotaxis ,Macrophages ,Monocyte ,Cell Biology ,Cell biology ,medicine.anatomical_structure ,chemistry ,Lysophosphatidylinositol ,RNA Interference ,Lysophospholipids - 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.
- Published
- 2021