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C10 Is a Novel Chemokine Expressed in Experimental Inflammatory Demyelinating Disorders that Promotes Recruitment of Macrophages to the Central Nervous System

https://doi.org/10.1016/S0002-9440(10)65370-9Get rights and content

Chemokines may be important in the control of leukocytosis in inflammatory disorders of the central nervous system. We studied cerebral chemokine expression during the evolution of diverse neuroinflammatory disorders in transgenic mice with astrocyte glial fibrillary acidic protein-targeted expression of the cytokines IL-3, IL-6, or IFN-α and in mice with experimental autoimmune encephalomyelitis. Distinct chemokine gene expression patterns were observed in the different central nervous system inflammatory models that may determine the phenotype and perhaps the functions of the leukocytes that traffic into the brain. Notably, high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis. In both these neuroinflammatory models, C10 RNA and protein expressing cells were predominantly macrophage/microglia and foamy macrophages present within demyelinating lesions as well as in perivascular infiltrates and meninges. Intracerebroventricular injection of recombinant C10 protein promoted the recruitment of large numbers of Mac-1+ cells and, to a much lesser extent, CD4+ lymphocytes into the meninges, choroid plexus, ventricles, and parenchyma of the brain. Thus, C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show, also acts as a potent chemotactic factor for the migration of these leukocytes to the brain.

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Supported by U. S. Public Health Service grants MH 47680 and MH 50426 (to I. L. C.). V.C.A. was supported by Fondation Singer Polignac (Paris) and is currently a postdoctoral fellow of the National Multiple Sclerosis Society. S. L. is supported by a NATO Postdoctoral Fellowship. A. P. was a postdoctoral fellow of the Deutsche Forschungsgmeinschaft (grant Pa 602/1–1).

Axel Pagenstecher's current address: Department of Neuropathology, University of Freiburg, Freiburg, Germany.

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