Top

Published in:

01-11-2003 | Regular Paper

Phase-dependent expression of matrix metalloproteinases and their inhibitors in demyelinating canine distemper encephalitis

Authors: Qin Miao, Wolfgang Baumgärtner, Klaus Failing, Susanne Alldinger

Published in: Acta Neuropathologica | Issue 5/2003

Abstract

Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent enzymes that cleave molecules of the extracellular matrix, and thus are able to open the blood-brain-barrier and affect myelin. Their inhibitors (TIMPs) are important candidates for the therapy of demyelinating diseases. To establish an immunohistochemical profile of MMP and TIMP expression in plaque variants in dogs with spontaneous demyelinating distemper encephalitis, paraffin-embedded cerebella were studied employing the avidin-biotin-peroxidase complex method with a panel of nine polyclonal (anti-MMP-1, -3, -7, -9, -12, -13, -14, -TIMP-1, and -2) and two monoclonal antibodies (anti-latent MMP-2, and -MMP-11). All MMPs and TIMPs were prominently up-regulated in acute and subacute non-inflammatory lesions, and double-labeling techniques showed that they were mainly expressed by astrocytes and brain macrophages/microglia. In subacute inflammatory and chronic plaques, a moderate to strong decrease of MMP and TIMP expression compared to acute lesions was observed. In these phases MMP-11, -12, and -13 were still moderately present. In addition to astro- and microglia, invading perivascular mononuclear cells were positive for MMPs and TIMPs. In summary, there seems to be a phase-dependent expression of MMPs and TIMPs in demyelinating canine distemper encephalitis, and an MMP-TIMP imbalance might account for the lesion progression in this disease.

Alldinger S, Baumgärtner W, Örvell C (1993) Restricted expression of viral surface proteins in canine distemper encephalitis. Acta Neuropathol 85:635–645PubMed

Alldinger S, Wünschmann A, Baumgärtner W, Voss C, Kremmer E (1996) Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis. Acta Neuropathol 92:273–280CrossRefPubMed

Alldinger S, Fonfara S, Kremmer E, Baumgärtner W (2000) Up-regulation of the hyaluronate receptor CD44 in canine distemper demyelinated plaques. Acta Neuropathol 99:138–146PubMed

Anthony DC, Miller KM, Fearn S, Townsend MJ, Opdenakker G, Wells GM, Clements JM, Chandler S, Gearing AJ, Perry VH (1998) Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS. J Neuroimmunol 87:62–72PubMed

Bever CT, Rosenberg GA (1999) Matrix metalloproteinases in multiple sclerosis—Targets of therapy or markers of injury? Neurology 53:1380–1381PubMed

Brew K, Dinakarpandian D, Nargase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267–283PubMed

Black RA, Rauch CT, Kozlosky CJ, et al (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-α from cells. Nature 385:729–732PubMed

Clements JM, Cossins JA, Wells GMA, Corkill DJ, Helfrich K, Wood LM, Pigott R, Stabler G, Ward GA, Gearing AJH, Miller KM (1997). Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-α inhibitor. J Neuroimmunol 74:85–94PubMed

Cuzner ML, Opdenakker G (1999) Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J Neuroimmunol 94:1–14CrossRefPubMed

10.

DalCanto MC, Rabinowitz SG (1982) Experimental models of virus-induced demyelination of the central nervous system. Ann Neurol 11:107–109PubMed

11.

Dixon WJ (1993) BMDP statistical software manual, vol 1 and 2. University of California Press, Berkeley

12.

Dubois B, Opdenakker G, Carton H (1999) Gelatinase B in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neurol Belg 99:53–56PubMed

13.

Gottschall PE, Deb S (1996) Regulation of matrix metalloproteinase expression in astrocytes, microglia and neurons. Neuroimmunomodulation 3:69–75PubMed

14.

Gottschall PE, Yu X (1995) Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 64:1513–1520PubMed

15.

Graber HU, Müller CF, Vandevelde M, Zurbriggen A (1995) Retsricted infection with canine distemper virus leads to down-regulation of myelin gene transcription in cultured oligodendrocytes. Acta Neuropathol 90:312–318CrossRefPubMed

16.

Gröne A, Alldinger S, Baumgärtner W (2000) Interleukin-1β, -6, -12 and tumor necrosis factor-α expression in brains of dogs with canine distemper virus infection. J Neuroimmunol 110:20–30CrossRefPubMed

17.

Hartung H-P, Kieseier, BC (2000) The role of matrix metalloproteinases in autoimmune damage to the central and peripheral nervous system. J Neuroimmunol 107:140–147PubMed

18.

Khuth S-T, Akaoka H, Pagenstecher A, Verlaeten O, Belin M-F, Giraudon P, Bernard A (2001) Morbillivirus infection of the mouse central nervous system induces region-specific upregulation of MMPs and TIMPs correlated to inflammatory cytokine expression. J Virol 75:8268–8282CrossRefPubMed

19.

Kieseier BC, Paul R, Koedel U, Seifert T, Clements JM, Gearing AJ, Pfister HW, Hartung HP (1999) Differential expression of matrix metalloproteinases in bacterial meningitis. Brain 122:1579–1587CrossRefPubMed

20.

Kieseier BC, Seifert T, Giovannoni G, Hartung H-P (1999) Matrix metalloproteinases in inflammatory demyelination—targets for treatment. Neurology 52:20–25

21.

Kouwenhoven M, Ozenci V, Gomes A, Yarilin D, Giedraitis V, Press R, Link H (2001) Multiple sclerosis: elevated expression of matrix metalloproteinases in blood monocytes. J Autoimmun 16:463–470CrossRefPubMed

22.

Leppert D, Ford J, Stabler G, Grygar C, Lienert C, Huber S, Miller KM, Hauser SL, Kappos L (1998) Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain 121:2327–2334CrossRefPubMed

23.

Liedtke W, Cannella B, Mazzaccaro RJ, Clements JM, Miller KM, Wucherpfennig KW, Gearing AJ, Raine CS (1998) Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Ann Neurol 44:35–46PubMed

24.

Lindberg RLP, De Groot CJA, Montagne L, Freitag P, Valk P van der, Kappos L, Leppert D (2001) The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain 124:1743–1753CrossRefPubMed

25.

Lo EH, Wang X, Cuzner ML (2002) Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases. J Neurosci Res 69:1–9CrossRefPubMed

26.

Markus S, Failing K, Baumgärtner W (2002) Increased expression of pro-inflammatory cytokines and lack of up-regulation of anti-inflammatory cytokines in early distemper CNS lesions. J Neuroimmunol 125:30–41CrossRefPubMed

27.

Matrisian LM (1990) Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121–125PubMed

28.

Matyszak MK, Perry VH (1996) Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases. J Neuroimmunol 69:141–149CrossRefPubMed

29.

McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they're not just for matrix anymore! Curr Opin Cell Biol 13:534–540

30.

Özenci V, Rinaldi L, Teleshova N, Matusevicius D, Kivisakk P, Kouwenhoven M, Link H (1999) Metalloproteinases and their tissue inhibitors in multiple sclerosis. J. Autoimmun 12:297–303CrossRef

31.

Pagenstecher A, Stalder AK, Kincaid CL, Shapiro SD, Campbell IL (1998) Differential expression of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states. Am J Pathol 152:729–741PubMed

32.

Pringle CR (1999) Virus taxonomy at the Xith International Congress of Virology, Sydney, Australia. Arch Virol 144:2065–2070CrossRefPubMed

33.

Ries C, Petrides PE (1995) Cytokine regulation of matrix metalloproteinase activity and its regulatory dysfunction in disease. Biol Chem Hoppe-Seyler 376:345–355

34.

Rosenberg GA (2001) Matrix metalloproteinases in multiple sclerosis: Is it time for a treatment trial. Ann Neurol 50:431–433CrossRefPubMed

35.

Rosenberg GA (2001) Matrix metalloproteinases in multiple sclerosis: Is it time for a treatment trial. Ann Neurol 50:431–433Rosenberg GA (2002) Matrix metalloproteinases in neuroinflammation. Glia 39:279–291CrossRefPubMed

36.

Rosenberg GA, Kornfeld M, Estrada E, Kelley RO Liotta LA, Stetler-Stevenson WG (1992) TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res 576:203–207PubMed

37.

Rosenberg GA, Cunningham LA, Wallace J (2001) Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res 893:104–112CrossRefPubMed

38.

Sekine-Aizawa Y, Hama E, Watanabe K, Tsubuki S, Kanai-Azuma M, Kanai Y, Arai H, Aizawa H, Iwata N, Saido TC (2001) Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain-specific MMP highly expressed in cerebellum. Eur J Neurosci 13:935–948CrossRefPubMed

39.

Stetler-Stevenson WG, Krutzsch HC, Liotta LA (1989) Tissue inhibitor of metalloproteinase (TIMP-2): a new member of the metalloproteinase inhibitor family. J Biol Chem 264:17374–17378PubMed

40.

Streit WJ, Kreutzberg GW (1987) Lectin binding by resting and reactive microglia. J Neurocytol 16:249–260PubMed

41.

Tipold A, Moore P, Zurbriggen A, Bürgener I, Barben G, Vandervelde M (1999) Early T cell response in the central nervous system in canine distemper virus infection. Acta Neuropathol 97:45–56CrossRefPubMed

42.

Wells GM, Catlin G, Cossins JA, Mangan M, Ward GA, Miller KM, Clements JM (1996) Quantitation of matrix metalloproteinases in cultured rat astrocytes using the polymerase chain reaction with a multi-competitor cDNA standard. Glia 18:332–340CrossRefPubMed

43.

Woessner JF (1991) Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 5:2145–2153PubMed

44.

Wünschmann A, Alldinger S, Kremmer E, Baumgärtner W (1999) Identification of CD4⁺ and CD8⁺ T cell subsets and B cells in the brain of dogs with spontaneous acute, subacute- and chronic-demyelinating distemper encephalitis. J Vet Immunol Immunopathol 67:101–116CrossRef

45.

Yong, VW, Krekoski CA, Forsyth PA, Bell R, Edwards DR (1998) Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 21:75–80PubMed

46.

Zurbriggen A, Schmid I, Graber HU, Vandevelde M (1998) Oligodendroglial pathology in canine distemper. Acta Neuropathol 95:71–77CrossRefPubMed

Title: Phase-dependent expression of matrix metalloproteinases and their inhibitors in demyelinating canine distemper encephalitis
Authors: Qin Miao
Wolfgang Baumgärtner
Klaus Failing
Susanne Alldinger
Publication date: 01-11-2003
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 5/2003
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-003-0754-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Phase-dependent expression of matrix metalloproteinases and their inhibitors in demyelinating canine distemper encephalitis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2003

Rosette-forming glioneuronal tumor of the fourth ventricle

PTEN methylation and expression in glioblastomas

Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue

Neuropathological analysis in spinal muscular atrophy type II

Distal effects in a model of proximal axonopathy: 3,3'-iminodipropionitrile causes specific loss of neurofilaments in rat vestibular afferent endings

Cellular localization of prolactin-releasing peptide receptors in the human pituitary