Recruitment of inflammatory cells to the central nervous system (CNS) through transgenic expression of fibroblast-induced cytokine (FIC)

FIC, a member of the "C-C" family of chemokincs, induces chemotaxis of monocytes in vitro . To study the effects of FIC in vivo . we constitutively expressed FIC' under the control of the myelin basic protein promoter in transgenic mice. CNS histologie changes, were characterized by perivascular cuffs containing predominantly mononuclear cells admixed with smaller numbers of neutrophils and apoptotic debris. The recruited ceîls were primarily in a perivascular orientation in the méninges, choroid plexus, and white matter with limited extension into the adjacent neuropil. The majority of the mononuclear cells were 12-15 urn in diameter, had an oval to reriiform nucleus, and contained a paucity of organelles. predominantly mitochondria with few cytocavitary profiles and Golgi apparatus. The nature and severity of the perivascular aggregates did not increase over time, nor induce a prominent glial reaction in the neuropil. Most of the infiltrating mononuclear cells stained positively with the macrophage marker F4/80, however, approximately 60% also stained positively for 7/4, a neutrophil marker. Extrane-nral lesions in the transgenic mice were limited to mild myeloid hyperplasia in the bone marrow. The results of this study indicate that the FIC protein is capable of directing monocyte recruitment m vivo . We are currently investigating whether the influx of neutrophils into the CNS of the transgenic mice is due to FIC expression or secondary to other factors.