Research Article| Volume 41, ISSUE 1, P29-34, November 1992

Download started.


Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological disorders

      This paper is only available as a PDF. To read, Please Download here.


      A substrate conversion assay was used to detect gelatinase activity in the cerebrospinal fluid (CSF) of patients with various neurological disorders. Two main forms of gelatinase with an apparent molecular mass of 65 and 85 kDa, respectively, could be discerned. The high molecular mass gelatinase was detectable only in samples of patients with multiple sclerosis or other inflammatory neurological disorders. A statistically significant correlation was found between the level of the 85-kDa gelatinase and the CSF cytosis. This protease could play a role in the process of demyelination and breakdown of the blood-brain barrier in certain neurological disorders, such as multiple sclerosis.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Neuroimmunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Alvord E.C.
        • Hruby S.
        • Sires L.R.
        Degradation of myelin basic protein by cerebrospinal fluid: preservation of antigenic determinants under physiological conditions.
        Ann. Neurol. 1979; 6: 474-482
        • Brosnan C.F.
        • Cammer W.
        • Norton W.T.
        • Bloom B.R.
        Proteinase inhibitors suppress the development of experimental allergic encephalomyelitis.
        Nature. 1980; 285: 235-237
        • Cammer W.
        • Bloom B.R.
        • Norton W.T.
        • Gordon S.
        Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: A possible mechanism of inflammatory demyelination.
        in: Proc. Natl. Acad. Sci. USA. 75. 1978: 1554-1558
        • Cuzner M.L.
        • Davison A.N.
        • Rudge P.
        Proteolytic enzyme activity of blood leukocytes and cerebrospinal fluid in multiple sclerosis.
        Ann. Neurol. 1978; 4: 337-344
        • Frei K.
        • Leist T.P.
        • Meager A.
        • Gallo P.
        • Leppert D.
        • Zinkernagel R.M.
        • Fontana A.
        Production of B cell stimulatory factor-2 and interferon-gamma in the central nervous system during viral meningitis and encephalitis.
        J. Exp. Med. 1988; 168: 449-453
        • Gijbels K.
        • Van Damme J.
        • Proost P.
        • Put W.
        • Carton H.
        • Billiau A.
        Interleukin 6 production in the central nervous system during experimental autoimmune encephalomyelitis.
        Eur. J. Immunol. 1990; 20: 233-235
        • Hallpike J.F.
        • Adams C.W.M.
        Proteolysis and myelin breakdown: a review of recent histochemical and biochemical studies.
        Histochem. J. 1969; 1: 559-578
        • Hauser S.L.
        • Doolittle T.H.
        • Lincoln R.
        • Brown R.H.
        • Dinarello C.A.
        Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6.
        Neurology. 1990; 40: 1735-1739
        • Heussen C.
        • Dowdle E.B.
        Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates.
        Anal. Biochem. 1980; 102: 196-202
        • Houssiau F.A.
        • Bukasa K.
        • Sindic C.J.M.
        • Van Damme J.
        • Van Snick J.
        Elevated levels of the 26K human hybridoma growth factor (interleukin-6) in cerebrospinal fluid of patients with acute infection of the central nervous system.
        Clin. Exp. Immunol. 1988; 71: 320-323
        • Inuzuka T.
        • Sato S.
        • Baba H.
        • Miyatake T.
        Neutral protease in cerebrospinal fluid from patients with multiple sclerosis and other neurological diseases.
        Acta Neurol. Scand. 1987; 76: 18-23
        • Inuzuka T.
        • Sato S.
        • Baba H.
        • Miyatake T.
        Suppressive effect of camostat mesilate (FOY 305) on acute experimental allergic encephalomyelitis (EAE).
        Neurochem. Res. 1988; 13: 225-228
        • Khoury S.J.
        • Weiner H.L.
        • Hafler D.A.
        Immunologic basis of multiple sclerosis.
        in: Handbook of Multiple Sclerosis. Marcel Dekker, New York, NY1990: 129-149
        • Link H.
        • Tibbling G.
        Principles of albumin and IgG analysis in neurological disorders. II. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis.
        Scand. J. Clin. Lab. Invest. 1977; 37: 397-401
        • Lotz M.
        • Guerne P.-A.
        Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA).
        J. Biol. Chem. 1991; 266: 2017-2020
        • Mackay A.R.
        • Hartzler J.L.
        • Pelina M.D.
        • Thorgeirsson U.P.
        Studies on the ability of 65-kDa and 92-kDa tumor cell gelatinases to degrade type IV collagen.
        J. Biol. Chem. 1990; 265: 21929-21934
        • Maimone D.
        • Gregory S.
        • Arnason B.G.W.
        • Reder A.T.
        Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis.
        J. Neuroimmunol. 1991; 32: 67-74
        • Masure S.
        • Opdenakker G.
        Cytokine-mediated proteolysis in tissue remodelling.
        Experientia. 1989; 45: 542-549
        • Masure S.
        • Billiau A.
        • Van Damme J.
        • Opdenakker G.
        Human hepatoma cells produced an 85 kDa gelatinase regulated by phorbol 12-myristate 13-acetate.
        Biochim. Biophys. Acta. 1990; 1054: 317-325
        • Masure S.
        • Proost P.
        • Van Damme J.
        • Opdenakker G.
        Purification and identification of 91-kDa neurophil gelatinase. Release by the activating peptide interleukin-8.
        Eur. J. Biochem. 1991; 198: 391-398
        • Matrisian L.M.
        Metalloproteinases and their inhibitors in matrix remodeling.
        Trends Genet. 1990; 6: 121-125
        • Opdenakker G.
        • Masure S.
        • Grillet B.
        • Van Damme J.
        Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis.
        Lymphokine Cytokine Res. 1991; 10: 317-324
        • Opdenakker G.
        • Masure S.
        • Proost P.
        • Billiau A.
        • Van Damme J.
        Natural human monocyte gelatinase and its inhibitor.
        FEBS Lett. 1991; 284: 73-78
        • Poser C.M.
        • Paty D.W.
        • Scheinberg L.
        • McDonald W.I.
        • Davis F.A.
        • Ebers G.C.
        • Johnson K.P.
        • Sibley W.A.
        • Silberberg D.H.
        • Tourtellotte W.W.
        New diagnostic criteria for multiple sclerosis: Guidelines for research protocols.
        Ann. Neurol. 1983; 13: 227-231
        • Raine C.S.
        Analysis of autoimmune demyelination: Its impact upon multiple sclerosis.
        Lab. Invest. 1984; 50: 608-635
        • Sato T.
        • Ito A.
        • Mori Y.
        Interleukin 6 enhances the production of tissue inhibitor of metalloproteinase (TIMP) but not that of matric metallopreteinase by human fibroblasts.
        Biochem. Biophys. Res. Commun. 1990; 170: 824-829
        • Tibbling G.
        • Link H.
        • Ohman S.
        Principles of albumin and IgG analysis in neurological disorders. I. Establishment of reference values.
        Scand. J. Clin. Lab. Invest. 1977; 37: 385-390
        • Vaes G.
        Cellular biology and biochemical mechanism of bone resorption. A review of recent developments on the formation, activation and mode of action of osteoclasts.
        Clin. Ortop. 1988; 231: 239-271
        • Van Damme J.
        • Opdenakker G.
        • Simpson R.J.
        • Rubira M.R.
        • Cayphas S.
        • Vink A.
        • Billiau A.
        • Van Snick J.
        Identification of the human 26-kD protein, Interferon β2 (IFN-β2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor.
        J. Exp. Med. 1987; 165: 914-919