| First Author | Kapellos TS | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 5 | Pages | 6154-6167 |
| PubMed ID | 30799631 | Mgi Jnum | J:291368 |
| Mgi Id | MGI:6444966 | Doi | 10.1096/fj.201802524R |
| Citation | Kapellos TS, et al. (2019) Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment. FASEB J 33(5):6154-6167 |
| abstractText | Cannabinoid receptor (CB)2 is an immune cell-localized GPCR that has been hypothesized to regulate the magnitude of inflammatory responses. However, there is currently no consensus as to the mechanism by which CB2 mediates its anti-inflammatory effects in vivo. To address this question, we employed a murine dorsal air pouch model with wild-type and CB2(-/-) 8-12-wk-old female and male C57BL/6 mice and found that acute neutrophil and lymphocyte antigen 6 complex, locus C(hi) monocyte recruitment in response to Zymosan was significantly enhanced in CB2(-/-) mice. Additionally, levels of matrix metalloproteinase 9 and the chemokines C-C motif chemokine ligand (CCL)2, CCL4, and C-X-C motif chemokine ligand 10 in CB2(-/-) pouch exudates were elevated at earlier time points. Importantly, using mixed bone marrow chimeras, we revealed that the proinflammatory phenotype in CB2(-/-) mice is neutrophil-intrinsic rather than stromal cell-dependent. Indeed, neutrophils isolated from CB2(-/-) mice exhibited an enhanced migration-related transcriptional profile and increased adhesive phenotype, and treatment of human neutrophils with a CB2 agonist blocked their endothelial transmigration. Overall, we have demonstrated that CB2 plays a nonredundant role during acute neutrophil mobilization to sites of inflammation and, as such, it could represent a therapeutic target for the development of novel anti-inflammatory compounds to treat inflammatory human diseases.-Kapellos, T. S., Taylor, L., Feuerborn, A., Valaris, S., Hussain, M. T., Rainger, G. E., Greaves, D. R., Iqbal, A. J. Cannabinoid receptor 2 deficiency exacerbates inflammation and neutrophil recruitment. |
