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

• DOI: 10.1016/j.bbrc.2021.06.090
• Publication Date: 2021-07-05T16:15:56Z
• Authors: Xiaojia Li; Kei Hanafusa; Madoka Kage; Noriko Yokoyama; Hitoshi Nakayama; Tomomi Hotta; Eriko Oshima; Koki Kano; Ichiro Matsuo; Yasuko Nagatsuka; Kenji Takamori; Hideoki Ogawa; Yoshio Hirabayashi; Kazuhisa Iwabuchi
• Keywords: 0301 basic medicine; THP-1 Cells; Chemotaxis; Macrophages; Blotting, Western; Monocytes; 3. Good health; 03 medical and health sciences; Glucosides; Cell Movement; Humans; RNA Interference; Lysophospholipids; Receptors, Cannabinoid

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.