Degradation of myelin basic protein by cerebrospinal fluid: Preservation of antigenic determinants under physiological conditions

Alvord, Ellsworth C.; Hruby, Sarka; Sires, L. R.

doi:10.1002/ana.410060604

Cited by 36 publications

(6 citation statements)

References 39 publications

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“…Further studies are required to determine the frequency of MBP-containing CIC in demyelinating and non-demyelinating diseases of the human nervous system. MBP in serum is fragmented by proteolytic enzymes and these fragments retain their antigenicity (Paterson 1976;Alvord et al, 1979). Soluble MBP fragments can form complexes of different lattice structure with anti-MBP and might exert immunoregulatory effects in MS (Paterson, 1982).…”

Section: Discussionmentioning

confidence: 99%

Myelin Basic Protein: A Component of Circulating Immune Complexes in Multiple Sclerosis

Dasgupta

Catz

Warren

et al. 1983

Can. j. neurol. sci.

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SUMMARY: Myelin basic protein (MBP) is an antigenic component of circulating immune complexes (CIC) in patients with multiple sclerosis (MS). Immune complexes were isolated from the sera by adsorption to Raji cells and then acid eluted. Final identification of MBP from Raji eluates was done by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by MBP radioimmunoassay (RIA) of gel eluates and by an immunoblot technique. RESUME: Les donnees recueillies ont permis d'etablir que la proteine basique de la myeline (MBP) est presente dans les complexes immuns circulants (CIC) de certains malades atteints de sclerose en plaques. Ces complexes ont ete isoles du serum par adsorption sur cellules de Raji et par elution en milieu acide. L'identification finale de la MBP a ete completee par radioimmunoassay et par une technique "immunoblot" apres electrophorese en gel de polyacrylamide-dodecyl de sodium (SDS-PAGE).

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Section: Discussionmentioning

confidence: 99%

Myelin Basic Protein: A Component of Circulating Immune Complexes in Multiple Sclerosis

Dasgupta

Catz

Warren

et al. 1983

Can. j. neurol. sci.

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“…Proteolytic events play a central role in many discrete steps culminating in inflammatory demyelination including immune cell activation, extravasation, proinflammatory cytokine and complement activation, demyelination as well as oligodendroglial and axon injury. Of the known protease families (including serine, metallo-and cysteine), there is documented involvement of each at one or more of these steps (3,9,11,17,22,25,27,35,41,57). Of all protease families studied with regard to MS, the matrix metalloprotease (MMP) family has historically received most attention.…”

Section: Introductionmentioning

confidence: 99%

Kallikrein 6 Regulates Early CNS Demyelination in a Viral Model of Multiple Sclerosis

Scarisbrick¹,

Yoon²,

Panos³

et al. 2012

Brain Pathology

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Kallikrein 6 (Klk6) is a secreted serine protease that is elevated in active multiple sclerosis lesions and patient sera. To further evaluate the involvement of Klk6 in chronic progressive demyelinating disease, we determined its expression in the brain and spinal cord of SJL mice infected with Theiler’s murine encephalomyelitis virus (TMEV) and assessed the effects of Klk6-neutralizing antibodies on disease progression. Klk6 RNA expression was elevated in the brain and spinal cord by 7 days post-infection (dpi). Thereafter, Klk6 expression persisted primarily in the spinal cord reaching a peak of 5-fold over controls at mid-chronic stages (60–120 dpi). Significant elevations in Klk6 RNA were also induced in splenocytes stimulated with viral capsid proteins in vitro and in activated THP-1 monocytes. Klk6-neutralizing antibodies reduced TMEV-driven brain and spinal cord pathology and DTH responses when examined at early chronic time points (40 dpi). Reductions in spinal cord pathology included a decrease in activated monocytes/microglia and reductions in the loss of myelin basic protein (MBP). By 180 dpi, pathology scores no longer differed between groups. These findings point to regulatory activities for Klk6 in the development and progression of CNS inflammation and demyelination that can be effectively targeted through the early chronic stages with neutralizing antibody.

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“…Furthermore, macrophages can secrete a large array of lytic enzymes (Chapman, 1991) and can also phagocytose myelin fragments. Since long, proteases are thought to be involved in myelin degradation, with indirect evidence pointing to neutral proteases (Cammer et al, 1978;Cuzner et al, 1978;Alvord et al, 1979;Smith and Benjamins, 1984;Inuzuka et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein

Gijbels

Proost

Masure

et al. 1993

J of Neuroscience Research

193

107

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Gelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non-induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood-brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders.

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Degradation of myelin basic protein by cerebrospinal fluid: Preservation of antigenic determinants under physiological conditions

Cited by 36 publications

References 39 publications

Myelin Basic Protein: A Component of Circulating Immune Complexes in Multiple Sclerosis

Myelin Basic Protein: A Component of Circulating Immune Complexes in Multiple Sclerosis

Kallikrein 6 Regulates Early CNS Demyelination in a Viral Model of Multiple Sclerosis

Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein

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