RT Journal Article
T1 The CB2 cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of animal model of multiple sclerosis
A1 Palazuelos Diego, Javier
A1 Davoust, Natalie
A1 Julien, Boris
A1 Hatterer, Eric
A1 Aguado Sánchez, Tania
A1 Benito Villalvilla, Cristina
A1 Mechoulam, Raphael
A1 Romero, Julián
A1 Silva, Augusto
A1 Guzmán Pastor, Manuel
A1 Nataf, Serge
A1 Galve Roperh, Ismael
AB Cannabinoids are potential agents for the development of therapeutic strategies against multiple sclerosis. Here we analyzed the role of the peripheral CB2 cannabinoid receptor in the control of myeloid progenitor cell trafficking toward the inflamed spinal cord and their contribution to microglial activation in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE). CB2 receptor knock-out mice showed an exacerbated clinical score of the disease when compared with their wild-type littermates, and this occurred in concert with extended axonal loss, T-lymphocyte (CD4+) infiltration, and microglial (CD11b+) activation. Immature bone marrow-derived CD34+ myeloid progenitor cells, which play a role in neuroinflammatory pathologies, were shown to express CB2 receptors and to be abundantly recruited toward the spinal cords of CB2 knock-out EAE mice. Bone marrow-derived cell transfer experiments further evidenced the increased contribution of these cells to microglial replenishment in the spinal cords of CB2-deficient animals. In line with these observations, selective pharmacological CB2 activation markedly reduced EAE symptoms, axonal loss, and microglial activation. CB2 receptor manipulation altered the expression pattern of different chemokines (CCL2, CCL3, CCL5) and their receptors (CCR1, CCR2), thus providing a mechanistic explanation for its role in myeloid progenitor recruitment during neuroinflammation. These findings demonstrate the protective role of CB2 receptors in EAE pathology; provide evidence for a new site of CB2 receptor action, namely the targeting of myeloid progenitor trafficking and its contribution to microglial activation; and support the potential use of non-psychoactive CB2 agonists in therapeutic strategies for multiple sclerosis and other neuroinflammatory disorders.
PB Elsevier
SN 0021-9258
YR 2008
FD 2008
LK https://hdl.handle.net/20.500.14352/91032
UL https://hdl.handle.net/20.500.14352/91032
LA eng
NO Palazuelos et al. The CB2 cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of animal model of multiple sclerosis. J Biol Chem. 283,13320-29 (2008)
NO Ministerio de Educación y Ciencia (España)
NO Comunidad  de Madrid
NO Universidad Complutense de Madrid
NO Fundación de Investigación Médica Mutua Madrileña Automovilística
NO Comunidad de Murcia
NO French embassy in Spain
NO French Association for Multiple Sclerosis Research
DS Docta Complutense
RD 20 abr 2025