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Titolo:
Plasminogen activators in multiple sclerosis lesions - Implications for the inflammatory response and axonal damage
Autore:
Gveric, D; Hanemaaijer, R; Newcombe, J; van Lent, NA; Sier, CFM; Cuzner, ML;
Indirizzi:
Univ Coll London, Dept Neurochem, Neuroinflammat Grp, Inst Neurol, London WC1N 1PJ, England Univ Coll London London England WC1N 1PJ eurol, London WC1N 1PJ, England TNO PG, Gaubius Lab, Leiden, Netherlands TNO PG Leiden NetherlandsTNO PG, Gaubius Lab, Leiden, Netherlands San Raffaele Sci Inst, DIBIT, Dept Mol Med, I-20132 Milan, Italy San Raffaele Sci Inst Milan Italy I-20132 Mol Med, I-20132 Milan, Italy
Titolo Testata:
BRAIN
, volume: 124, anno: 2001,
parte:, 10
pagine: 1978 - 1988
SICI:
0006-8950(200110)124:<1978:PAIMSL>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN-TUMORS; EXTRACELLULAR-MATRIX; GELATINASE-B; RHEUMATOID-ARTHRITIS; CEREBROSPINAL-FLUID; IMMUNOCAPTURE ASSAY; ENDOTHELIAL-CELLS; TISSUE; EXPRESSION;
Keywords:
axon; ELISA; matrix metalloproteases; multiple sclerosis; plasminogen activators;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Gveric, D Univ Coll London, Dept Neurochem, Neuroinflammat Grp, Inst Neurol, 1 Wakefield St, London WC1N 1PJ, England Univ Coll London 1 Wakefield StLondon England WC1N 1PJ England
Citazione:
D. Gveric et al., "Plasminogen activators in multiple sclerosis lesions - Implications for the inflammatory response and axonal damage", BRAIN, 124, 2001, pp. 1978-1988

Abstract

Components of the plasminogen activator (PA) and matrix metalloprotease (MMP) cascade have been characterized in multiple sclerosis lesions by immunohistochemistry, enzyme-linked immunosorbent assay and enzyme activity assays in order to establish a functional role for the enzyme sequence in lesiondevelopment. Highly significant quantitative increases in urokinase PA (uPA), urokinase receptor (uPAR) and plasminogen activator inhibitor-1 were detected in acute multiple sclerosis lesions (P < 0.0001) and in uPAR in normal-appearing white matter (P < 0.0001) compared with control tissue. All three proteins were immunolocalized to mononuclear cells in perivascular cuffs and to macrophages in the lesion parenchyma. MMP-9 and the tissue inhibitor of metalloprotease-1 also increased during lesion development but the enzyme was present largely in the inactive pro-form. In contrast to uPA, the concentration and activity of tissue PA (WA), the most abundant plasminogenactivator in normal control brain, were reduced in multiple sclerosis specimens. In acute lesions tPA colocalized with fibrin(ogen) on large diameteraxons also stained with SMI-32, an immunohistochemical marker of axonal damage. The uPA-uPAR complex, concentrated on inflammatory cells in the perivascular zone of the evolving lesion, may facilitate cellular infiltration into the CNS which is amplified by MMP-mediated degradation of blood vessel matrix. tPA localization on injured axons may be a marker of axonal damage or represent a protective mechanism aimed at removal of fibrin deposits andrestoration of axonal function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 13:26:20