Similar pattern of MCP-1 expression in spinal cords and eyes of Lewis rats with experimental autoimmune encephalomyelitis associated anterior uveitis

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family responsible for the recruitment of T cells that have been found during inflammation of the spinal cord in experimental autoimmune encephalomyelitis (EAE) in Lewis rats immunized with myelin basic protein (MBP). Lewis rats injected with MBP also developed anterior uveitis (AU), which coincided with the onset of EAE. In the present studies, we examined the expression and distribution of MCP-1 in the eye and spinal cord during disease and compared it to the expression of Th1 cell type cytokines. Initially, MCP-1 expression was detected at the preclinical phase in the iris/ciliary body and lumbar spinal cord and increased during the course of EAE/AU. Mononuclear infiltrating cells and endothelial cells and astrocytes of the CNS could be identified as a source of MCP-1 by in situ hybridization. Kinetics of expression of Th1 characteristic cytokines such as IL-2 and IFNgamma was in agreement with the expression of MCP-1 chemokine. Moreover, induction of the gene expression of MCP-1 seemed to occur earlier than that of MIP-2, and it correlated with increasing disease severity. MCP-1 seems to contribute to the initial recruitment of inflammatory cells into both the tissues of the eye and CNS over the course of disease.

The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis

“…As these cells form the first line of defense in the BBB [69], their expression of CCL2 might strongly influence incipient steps of neuroinflammation [70]. Indeed, elevated CCL2 expression by BMEC has been reported in MS [71] and EAE [55,56], as well as in autoimmune inflammation of the peripheral nervous system [3]. Furthermore, intravenously administered anti-CCL2 antibody blocked heightened leukocyte adhesion to pial venular endothelium in vivo in mice suffering acute EAE [72], as well as prevented recurring clinical episodes in a chronic relapsing EAE model [73], possibly by antagonizing CCL2 at the luminal endothelial surface.…”

Intrathecal Fas Ligand Infusion Strengthens Immunoprivilege of Central Nervous System and Suppresses Experimental Autoimmune Encephalomyelitis

“…Those initially infiltrating T cells make contact with perivascular macrophages (10) and small numbers of infiltrating macrophages (11), which may present CNS Ags released during normal turnover. This Ag-specific recognition not only retains the infiltrating T cells (7), but also results in the production of proinflammatory cytokines and chemokines, which are responsible for the later large-scale homing and recruitment of inflammatory cells into the CNS (12,13). We hypothesized that elimination of initially infiltrating Ag-specific T cells and activated macrophages in CNS during this preclinical period could prevent the homing and recruitment of inflammatory cells, and therefore suppress acute EAE.…”

Chemokines and peripheral nerve demyelination

“…In many PNS diseases, even in non-in¯ammatory PNS diseases like hereditary polyneuropathy, ischemic neuropathy or axonal degeneration after sciatic nerve transection, mononuclear cell in®ltration is involved during the development of pathological changes (Cornblath et al, 1990;Venezie et al, 1995). Since CK play a pivotal role in leukocyte traf®cking into the CNS (Proost et al, 1996;Baggiolini, 1998), it has been hypothesized that they play a similar role in the PNS (Adamus et al, 1997;Eng et al, 1996;Godiska et al, 1995;Karpus et al, 1995;Glabinski et al, 1997;Ransohoff et al, 1996). The PNS is comprised of relatively fewer cell elements than the CNS: Schwann cells, peripheral nerve axons, ®broblasts, endothelia, pericytes and macrophages (Thomas et al, 1993).…”

“…Monocyte chemoattractant protein (MCP)-1 production in experimental allergic neuritis MCP-1, a well characterized b-chemokine, is produced by many cell lineages including monocytes, macrophages, lymphocytes, ®broblasts, endothelia, epithelia (Struyf et al, 1998;Douglas et al, 1997), and astrocytes (Adamus et al, 1997;Glabinski et al, 1997;Sun et al, 1997). Its target cells are monocytes, T lymphocytes and NK cells, but not neutrophils (Gu et al, 1997;Schall, 1994;Vaddi et al, 1997) and while a role for MCP-1 in EAE has been proposed (Karpus, 1995) its potential role in experimental allergic neuritis (EAN) has yet to be fully explored.…”