PMID- 8957442
OWN - NLM
STAT- MEDLINE
DCOM- 19970108
LR  - 20190512
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 55
IP  - 12
DP  - 1996 Dec
TI  - The expression of tissue-type plasminogen activator, matrix metalloproteases and 
      endogenous inhibitors in the central nervous system in multiple sclerosis: 
      comparison of stages in lesion evolution.
PG  - 1194-204
AB  - The expression of tissue-type plasminogen activator (t-PA) and a number of 
      metalloproteases as well as plasminogen activator inhibitor-1 (PAI-1) and tissue 
      inhibitor of metalloproteases-1 (TIMP-1) was analyzed in the central nervous 
      system (CNS) of normal control and multiple sclerosis (MS) cases by 
      immunohistopathology. The expression of t-PA was detectable only in the blood 
      vessel matrix in control white matter, but positive infiltrating mononuclear 
      cells were also observed in MS white matter and primary lesions. In active 
      plaques this pattern converted to strong positivity of foamy macrophages in areas 
      of demyelination, declining in chronic lesions. In general PAI-1 expression 
      paralleled that of t-PA. Gelatinase A and B were detected predominantly in 
      astrocytes and microglia throughout normal control white matter, with additional 
      positive mononuclear cells in perivascular cuffs in MS white matter. In the 
      demyelinating lesion there is widespread prominent expression of gelatinase B in 
      reactive astrocytes and macrophages, which persists in astrocytes in the chronic 
      lesion. TIMP-1 was also present in the vessel matrix and in lesional macrophages. 
      These observations on the coexpression of enzymes and inhibitors of the matrix 
      degrading cascade in CNS tissue pinpoint t-PA, a rate-limiting enzyme, and 
      gelatinase B as therapeutic targets in MS.
FAU - Cuzner, M L
AU  - Cuzner ML
AD  - Multiple Sclerosis Laboratory, Institute of Neurology, London, UK.
FAU - Gveric, D
AU  - Gveric D
FAU - Strand, C
AU  - Strand C
FAU - Loughlin, A J
AU  - Loughlin AJ
FAU - Paemen, L
AU  - Paemen L
FAU - Opdenakker, G
AU  - Opdenakker G
FAU - Newcombe, J
AU  - Newcombe J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Glycoproteins)
RN  - 0 (Myelin Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Central Nervous System/*metabolism/pathology
MH  - Disease Progression
MH  - Enzyme Induction
MH  - Female
MH  - Gene Expression
MH  - Glycoproteins/*biosynthesis/genetics
MH  - Humans
MH  - In Situ Hybridization
MH  - Male
MH  - Metalloendopeptidases/*biosynthesis/genetics
MH  - Middle Aged
MH  - Multiple Sclerosis/*metabolism/pathology
MH  - Myelin Proteins/*metabolism
MH  - Nerve Tissue Proteins/*biosynthesis/genetics
MH  - Plasminogen Activator Inhibitor 1/*biosynthesis/genetics
MH  - RNA, Messenger/analysis
MH  - Tissue Inhibitor of Metalloproteinases
MH  - Tissue Plasminogen Activator/*biosynthesis/genetics
EDAT- 1996/12/01 00:00
MHDA- 1996/12/01 00:01
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 1996/12/01 00:01 [medline]
PHST- 1996/12/01 00:00 [entrez]
AID - 10.1097/00005072-199612000-00002 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 1996 Dec;55(12):1194-204. doi: 
      10.1097/00005072-199612000-00002.