Macrophage-independent T cell infiltration to the site of injury-induced brain inflammation.
We have addressed the role of macrophages in glial response and T cell entry to the CNS after axonal injury, by using intravenous injection of clodronate-loaded mannosylated liposomes, in C57BL6 mice. As expected, clodronate-liposome treatment resulted in depletion of peripheral macrophages which was confirmed by F4/80- and MOMA-1(-) stainings in spleen. Sequential clodronate-liposome treatment 4, 2 and 0 days before axotomy resulted in significant reduction of infiltrating CD45(high) CD11b+ macrophages in the hippocampus at 1, 2 and 3 days post-lesion, measured by flow cytometry. There was a slight delay in the expansion of CD45(dim) CD11+ microglia in clodronate-liposome treated mice, but macrophage depletion had no effect on the percentage of infiltrating T cells in the lesion-reactive hippocampus. Lesion-induced TNFalpha mRNA expression was not affected by macrophage depletion, suggesting that activated glial cells are the primary source of this cytokine in the axonal injury-reactive brain. This identifies a potentially important distinction from inflammatory autoimmune infiltration in EAE, where macrophages are a prominent source of TNFalpha and their depletion prevents parenchymal T cell infiltration and disease.
Fux
Michaela
M
Medical Biotechnology Center, University of Southern Denmark, Winsloewparken 25, DK-5000 Odense C, Denmark.
van Rooijen
Nico
N
Owens
Trevor
T
D000818:Animals; D019771:Axotomy; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004002:Clodronic Acid / Q000494:pharmacology; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006624:Hippocampus / Q000276:immunology / Q000293:injuries* / Q000473:pathology; D008081:Liposomes; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D050071:Bone Density Conservation Agents; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid