First Author | Bang S | Year | 2018 |
Journal | J Clin Invest | Volume | 128 |
Issue | 8 | Pages | 3568-3582 |
PubMed ID | 30010619 | Mgi Jnum | J:264697 |
Mgi Id | MGI:6193498 | Doi | 10.1172/JCI99888 |
Citation | Bang S, et al. (2018) GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain. J Clin Invest 128(8):3568-3582 |
abstractText | The mechanisms of pain induction by inflammation have been extensively studied. However, the mechanisms of pain resolution are not fully understood. Here, we report that GPR37, expressed by macrophages (MPhis) but not microglia, contributes to the resolution of inflammatory pain. Neuroprotectin D1 (NPD1) and prosaptide TX14 increase intracellular Ca2+ (iCa2+) levels in GPR37-transfected HEK293 cells. NPD1 and TX14 also bind to GPR37 and cause GPR37-dependent iCa2+ increases in peritoneal MPhis. Activation of GPR37 by NPD1 and TX14 triggers MPhi phagocytosis of zymosan particles via calcium signaling. Hind paw injection of pH-sensitive zymosan particles not only induces inflammatory pain and infiltration of neutrophils and MPhis, but also causes GPR37 upregulation in MPhis, phagocytosis of zymosan particles and neutrophils by MPhis in inflamed paws, and resolution of inflammatory pain in WT mice. Mice lacking Gpr37 display deficits in MPhi phagocytic activity and delayed resolution of inflammatory pain. Gpr37-deficient MPhis also show dysregulations of proinflammatory and antiinflammatory cytokines. MPhi depletion delays the resolution of inflammatory pain. Adoptive transfer of WT but not Gpr37-deficient MPhis promotes the resolution of inflammatory pain. Our findings reveal a previously unrecognized role of GPR37 in regulating MPhi phagocytosis and inflammatory pain resolution. |