Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier.
The contribution of peripheral macrophage was assessed in cuprizone intoxication, a model of demyelination and remyelination in which the blood-brain barrier remains intact. Flow cytometry of brain cells isolated from cuprizone-treated mice revealed an increase in the percentage of Mac-1(+)/CD45(hi) peripheral macrophage. To confirm these results in situ, C57BL/6 mice were lethally irradiated, transplanted with bone marrow from GFP-transgenic mice, and exposed to cuprizone. GFP(+) peripheral macrophages were seen in the CNS after 2 weeks of treatment, and infiltration continued through 6 weeks. While the peripheral macrophages were far outnumbered by the resident microglia, their recruitment across the blood-brain barrier alludes to a potentially important role.
McMahon
Eileen J
EJ
Department of Microbiology and Immunology, University of North Carolina, 27599, Chapel Hill, NC, USA
Suzuki
Kinuko
K
Matsushima
Glenn K
GK
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000276:immunology; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017493:Leukocyte Common Antigens / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011828:Radiation Chimera
D017252:CD3 Complex; D016177:Macrophage-1 Antigen; D017493:Leukocyte Common Antigens