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Cannabinoid CB2 Receptor Agonists Attenuate Leukocyte/Endothelium Interaction In An Experimental Autoimmune Encephalomyelitis Model
Author(s) -
Zhang Ming,
Martin Billy R,
Ni Xiang,
Adler Martin W,
Jallo Jack,
Tuma Ronald F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1158-c
Subject(s) - experimental autoimmune encephalomyelitis , cannabinoid receptor , cannabinoid receptor type 2 , intravital microscopy , cannabinoid , immune system , medicine , receptor , immunology , endothelium , encephalomyelitis , multiple sclerosis , pharmacology , agonist , chemistry , microcirculation
Leukocyte rolling and firm adhesion along brain and spinal cord microvascular endothelium are essential steps in the progress of Multiple Sclerosis (MS). The cannabinoid CB 2 receptor is primarily expressed by cells of the immune system and CB 2 receptor activation has been show to down‐regulate immune responses. The purpose of this investigation was to determine if selective CB 2 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 CB 2 agonists (0–3853 or 0–1966) were given on the 7 th 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 CB 2 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/mm 2 , 0–3853:6/mm 2 ) but also attenuate clinical symptoms. Funded by the Pennsylvania Department of Health and DA P30 13429.