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oligodendrocyte-associated metalloprotease
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A myelin / oligodendrocyte-associated metalloprotease Paul Glynn
MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK Myelination in the central nervous system involves interactions between oligodendrocytes, the extracellular matrix and axons; however, few molecules mediating this process have been characterised. A better understanding of myelination may indicate why remyelination fails in multiple sclerosis. Our studies on proteins in isolated myelin membrane preparations led to the identification of a novel myelin/oligodendrocyte-associated metalloprotease (MOM). The cDNA sequence of MOM suggests that it may be involved in cell-cell and cell-extracellular matrix interactions. We now aim to quantify MOM expression relative to periods of myelination and to identify molecules with which MOM interacts.
The hypothalamo-pituitary-adrenal axis in experimental allergic encephalomyelitis: activation and apoptosis Terence Smith a, Adrian K. Hewson a, Mascha Schmied b, Hans Lassman b, Louise Cuzner a
Multiple Sclerosis Laboratory, Institute of Neurology, 1 Wakefield Street, London WCIN 1PJ, UK, b Research Unit of Experimental Neuropathology, Austrian Academy of Sciences, Henna, Austria
a
Interactions between the immune and neuroendocrine (HPA axis) compartments are necessary to initiate recovery from and confer resistance to experi-
mental allergic encephalomyelitis (EAE), a T cell mediated inflammatory demyelinating disease. We have shown, using in vivo microdialysis, that the profile of hypothalamic mediators of adrenocortical activation (PGE z and cAMP) and magnitude of the corticosterone response following endotoxin or IL-lfl differ in EAE susceptible (Lewis) and resistant (Fisher) rat strains. Furthermore, we have found that whilst intact Lewis rats exhibit the normal course of EAE after inoculation with myelin basic protein-reactive T cells, adrenalectomised rats exhibit a fatal paralysis that is concomitant with reduced T cell apoptosis in the CNS.
Effector T cell mechanisms in experimental autoimmune uveoretinitis (EAU) V.L. Calder, M. McLauchlin, Z.S. Zhao, S.L. Lightman Institute of Ophthalmology, London, UK Posterior uveitis, like multiple sclerosis, is a disease of the central nervous system with a putative autoimmune aetiology. Immunohistochemical studies have shown an enhanced class II expression in the retina and an infiltration of CD4 + T cells. In order to understand the effector mechanisms of CD4 + T cells, the experimental model EAU was used. We have established retinal SAg-specific CD4 + T cell lines and clones and have examined the kinetics of lymphokine mRNA expression and production following activation. Using PCR, IL-2, IFNy, IL-4 and IL-10 mRNA were detected and IL-2 and IFNy produced. The role of these lymphokines in vivo and the implications for immunotherapy will be discussed.
A myelin / oligodendrocyte-associated metalloprotease Paul Glynn
MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK Myelination in the central nervous system involves interactions between oligodendrocytes, the extracellular matrix and axons; however, few molecules mediating this process have been characterised. A better understanding of myelination may indicate why remyelination fails in multiple sclerosis. Our studies on proteins in isolated myelin membrane preparations led to the identification of a novel myelin/oligodendrocyte-associated metalloprotease (MOM). The cDNA sequence of MOM suggests that it may be involved in cell-cell and cell-extracellular matrix interactions. We now aim to quantify MOM expression relative to periods of myelination and to identify molecules with which MOM interacts.
The hypothalamo-pituitary-adrenal axis in experimental allergic encephalomyelitis: activation and apoptosis Terence Smith a, Adrian K. Hewson a, Mascha Schmied b, Hans Lassman b, Louise Cuzner a
Multiple Sclerosis Laboratory, Institute of Neurology, 1 Wakefield Street, London WCIN 1PJ, UK, b Research Unit of Experimental Neuropathology, Austrian Academy of Sciences, Henna, Austria
a
Interactions between the immune and neuroendocrine (HPA axis) compartments are necessary to initiate recovery from and confer resistance to experi-
mental allergic encephalomyelitis (EAE), a T cell mediated inflammatory demyelinating disease. We have shown, using in vivo microdialysis, that the profile of hypothalamic mediators of adrenocortical activation (PGE z and cAMP) and magnitude of the corticosterone response following endotoxin or IL-lfl differ in EAE susceptible (Lewis) and resistant (Fisher) rat strains. Furthermore, we have found that whilst intact Lewis rats exhibit the normal course of EAE after inoculation with myelin basic protein-reactive T cells, adrenalectomised rats exhibit a fatal paralysis that is concomitant with reduced T cell apoptosis in the CNS.
Effector T cell mechanisms in experimental autoimmune uveoretinitis (EAU) V.L. Calder, M. McLauchlin, Z.S. Zhao, S.L. Lightman Institute of Ophthalmology, London, UK Posterior uveitis, like multiple sclerosis, is a disease of the central nervous system with a putative autoimmune aetiology. Immunohistochemical studies have shown an enhanced class II expression in the retina and an infiltration of CD4 + T cells. In order to understand the effector mechanisms of CD4 + T cells, the experimental model EAU was used. We have established retinal SAg-specific CD4 + T cell lines and clones and have examined the kinetics of lymphokine mRNA expression and production following activation. Using PCR, IL-2, IFNy, IL-4 and IL-10 mRNA were detected and IL-2 and IFNy produced. The role of these lymphokines in vivo and the implications for immunotherapy will be discussed.