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Myelin palingenesis: Further characterization
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BLOOD LYMPHOCYTE B-ADRENERGIC RECEPTORS IN MULTIPLE SCLEROSIS Barry G.W. Arnason, Margaret Brown, Anthony Reder, Ricardo Maselli Department of Neurology, University of Chicago, Chicago, l l l i n o i s MS may commence as a relapsing-remitting disease and become progressive later. What determines the switch to progression is not known. We postulate that a "strategic hit" within the CNS may a l t e r neural input to the immune system and determine subsequent course. T8+ cell-mediated suppressor (S) function is s i g n i f i c a n t l y deranged in progressive MS. The sympathetic nervous system (SNS) down-modulates immune response. In mice, SNS ablation is followed by upregulation of ~-adrenergic receptors on l~nnphocytes and by decreased S function. SNS function is compromised in progressive MS. Pedal SNS responses to e l e c t r i c a l stimulation were absent in 11 of 24 progressive MS cases versus 0 of 24 controls (p <.001). ~-adrenergic receptors on peripheral blood mononuclear c e l l s were 20.2 ± 4.5 pM/6 x lO b c e l l s (n=8) in MS versus 9.2 ± 1.0 for 8 age-matched controls (p <.04). T8+ cell values were 18.4 ± 4.2 for MS (n=7) and 5.5 ± 0.51 for 7 controls (p <.01). T4+ cell values were 4.1 ± 0.83 in MS and 2.1 ± 0.33 in controls (p <.03). B cell values were 49.4 ± 14.1 in MS and 42.4 ± 2.5 in controls ( n . s . ) . ~-adrenergic receptors on lymphoid c e l l s are upregulated in progressive MS. Loss of SNS input to the immune system may perturb immune regulation and a l t e r disease course. ~fYELIN PALINGENESIS: Dimitrios Arvanitis,
FURTHER CHARACTERIZATION
Marc Dumas and Sara Szuchet
The University of Chicago,
Chicago,
Iii. 60637
We have previously shown that mature oligodendrocytes (OLG) in long-term culture and in the absence of neurons assemble multilamellar structures (myelin palingenesis; Szuchet et al, Dev. Neurosc. 8: 208-221, 1986); but to do so, they require a signal. In vitro, this signal is transduced via OLO-substratum interaction; i.e., the substratum may act as a surrogate for neurons. To gain information on the three-dimensional conformation of these structures, OLG-cultures were processed for EM and thin sectioned serially. Preliminary image reconstruction suggested that these structures have the overall shape of a prolate ellipsoid of revolution. Computer assisted image reconstruction, now in progress, should provide insight into the manner these structures originate from cell soma and/or processes and the organization of individual lamella. Immunocytochemical characterization of the membranous structures, at the EM level, using the immunogold method, revealed the presence of all the major myelin proteins. Myelin basic protein and 2',3' cyclic nucleotide phosphodiesterase are both localized on the cytoplasmic side of the lamella. PLP can be detected on the surface because of its extracellular domain. The structures also carry on their surface galactocerebroside, a major OLG/myelin glycolipid. In addition, these structures stained with mAb VIII-8B9 directed against an, as yet, unidentified surface lipid specific to OLG/myelin (Dumas et al, unpublished). In summary, the membranous structures assembled by mature OLG in culture resemble structurally and compositionally myelin and should serve as a good model to study myelin assembly. Supported by grant RG-1223-C4 from the Nat. MS Soc. First Choice: Second Choice:
Glia-Neuron Interactions Neuronal Cell Markers in Health and Disease.
BLOOD LYMPHOCYTE B-ADRENERGIC RECEPTORS IN MULTIPLE SCLEROSIS Barry G.W. Arnason, Margaret Brown, Anthony Reder, Ricardo Maselli Department of Neurology, University of Chicago, Chicago, l l l i n o i s MS may commence as a relapsing-remitting disease and become progressive later. What determines the switch to progression is not known. We postulate that a "strategic hit" within the CNS may a l t e r neural input to the immune system and determine subsequent course. T8+ cell-mediated suppressor (S) function is s i g n i f i c a n t l y deranged in progressive MS. The sympathetic nervous system (SNS) down-modulates immune response. In mice, SNS ablation is followed by upregulation of ~-adrenergic receptors on l~nnphocytes and by decreased S function. SNS function is compromised in progressive MS. Pedal SNS responses to e l e c t r i c a l stimulation were absent in 11 of 24 progressive MS cases versus 0 of 24 controls (p <.001). ~-adrenergic receptors on peripheral blood mononuclear c e l l s were 20.2 ± 4.5 pM/6 x lO b c e l l s (n=8) in MS versus 9.2 ± 1.0 for 8 age-matched controls (p <.04). T8+ cell values were 18.4 ± 4.2 for MS (n=7) and 5.5 ± 0.51 for 7 controls (p <.01). T4+ cell values were 4.1 ± 0.83 in MS and 2.1 ± 0.33 in controls (p <.03). B cell values were 49.4 ± 14.1 in MS and 42.4 ± 2.5 in controls ( n . s . ) . ~-adrenergic receptors on lymphoid c e l l s are upregulated in progressive MS. Loss of SNS input to the immune system may perturb immune regulation and a l t e r disease course. ~fYELIN PALINGENESIS: Dimitrios Arvanitis,
FURTHER CHARACTERIZATION
Marc Dumas and Sara Szuchet
The University of Chicago,
Chicago,
Iii. 60637
We have previously shown that mature oligodendrocytes (OLG) in long-term culture and in the absence of neurons assemble multilamellar structures (myelin palingenesis; Szuchet et al, Dev. Neurosc. 8: 208-221, 1986); but to do so, they require a signal. In vitro, this signal is transduced via OLO-substratum interaction; i.e., the substratum may act as a surrogate for neurons. To gain information on the three-dimensional conformation of these structures, OLG-cultures were processed for EM and thin sectioned serially. Preliminary image reconstruction suggested that these structures have the overall shape of a prolate ellipsoid of revolution. Computer assisted image reconstruction, now in progress, should provide insight into the manner these structures originate from cell soma and/or processes and the organization of individual lamella. Immunocytochemical characterization of the membranous structures, at the EM level, using the immunogold method, revealed the presence of all the major myelin proteins. Myelin basic protein and 2',3' cyclic nucleotide phosphodiesterase are both localized on the cytoplasmic side of the lamella. PLP can be detected on the surface because of its extracellular domain. The structures also carry on their surface galactocerebroside, a major OLG/myelin glycolipid. In addition, these structures stained with mAb VIII-8B9 directed against an, as yet, unidentified surface lipid specific to OLG/myelin (Dumas et al, unpublished). In summary, the membranous structures assembled by mature OLG in culture resemble structurally and compositionally myelin and should serve as a good model to study myelin assembly. Supported by grant RG-1223-C4 from the Nat. MS Soc. First Choice: Second Choice:
Glia-Neuron Interactions Neuronal Cell Markers in Health and Disease.