Cannabinoid CB2 Receptor Agonists Attenuate Leukocyte/Endothelium Interaction In An Experimental Autoimmune Encephalomyelitis Model

Abstract

Leukocyte rolling and firm adhesion along brain and spinal cord microvascular endothelium are essential steps in the progress of Multiple Sclerosis (MS). The cannabinoid CB2 receptor is primarily expressed by cells of the immune system and CB2 receptor activation has been show to down-regulate immune responses. The purpose of this investigation was to determine if selective CB2 agonists (0-3853 or 0-1966) interfere with leukocyte rolling/adhesion and attenuate the progress of MS. The experiment was performed in an experimental autoimmune encephalomyelitis (EAE) model using C57BL/6 mice. EAE was induced by mouse myelin oligodentrocyte protein and pertussis toxin. Vehicle and one of the two CB2 agonists (0–3853 or 0–1966) were given on the 7th day after induction and every four days thereafter at 1mg/kg i.p. Leukocyte/ endothelial interaction was evaluated from a cranial window using an intravital microscopy. Motor function was examined daily. The results demonstrate that EAE exaggerates leukocyte/endothelial interaction in brain microvessels and CB2 agonists not only decrease the number of rolling leukocytes (vehicle: 20/min, 0–3853:13/min, 0–1966:7/min) and adhesive leukocytes (vehicle: 41/mm2, 0–3853:6/mm2) but also attenuate clinical symptoms. Funded by the Pennsylvania Department of Health and DA P30 13429.