PMID- 10482270
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20191024
IS  - 0364-5134 (Print)
IS  - 0364-5134 (Linking)
VI  - 46
IP  - 3
DP  - 1999 Sep
TI  - Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with 
      human immunodeficiency virus dementia.
PG  - 391-8
AB  - Pathological evidence suggests that alterations of the blood-brain barrier (BBB) 
      may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). 
      Increased BBB permeability could contribute to the development of dementia by 
      facilitating the entry of activated and infected monocytes, as well as 
      potentially toxic serum proteins, into the central nervous system. One mechanism 
      by which BBB permeability may be altered is through increased activity of select 
      matrix metalloproteinases (MMPs). In the present study, we examined the 
      possibility that MMPs that target critical BBB proteins, including laminin, 
      entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of 
      patients with HIVD. We also examined the possibility that such MMPs could be 
      produced by brain-derived cells, and that MMP production by these cells might be 
      increased by tumor necrosis factor-alpha, an inflammatory cytokine that is 
      produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using 
      western blot and enzyme-linked immunosorbent assay, we observed that CSF levels 
      of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, 
      through the use of gelatin substrate zymography, a sensitive functional assay for 
      MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently 
      detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF 
      from either nondemented seropositive (2/11) or seronegative (0/11) controls. 
      Although the presence of MMPs in the serum could contribute to elevated levels in 
      the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that 
      such release is increased after their stimulation with tumor necrosis 
      factor-alpha. Together, these results suggest that elevated CSF levels of select 
      MMPs may reflect immune activation within the central nervous system. They also 
      suggest that further studies may be warranted to determine whether these proteins 
      may play a role in the development of symptomatic neurological disease.
FAU - Conant, K
AU  - Conant K
AD  - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, 
      USA.
FAU - McArthur, J C
AU  - McArthur JC
FAU - Griffin, D E
AU  - Griffin DE
FAU - Sjulson, L
AU  - Sjulson L
FAU - Wahl, L M
AU  - Wahl LM
FAU - Irani, D N
AU  - Irani DN
LA  - eng
GR  - AI35042/AI/NIAID NIH HHS/United States
GR  - NS26643/NS/NINDS NIH HHS/United States
GR  - RR00722/RR/NCRR NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - AIDS Dementia Complex/*cerebrospinal fluid
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Collagenases/*cerebrospinal fluid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gelatinases/*cerebrospinal fluid
MH  - Humans
MH  - Matrix Metalloproteinase 2
MH  - Matrix Metalloproteinase 7
MH  - Matrix Metalloproteinase 9
MH  - Metalloendopeptidases/*cerebrospinal fluid
MH  - Prospective Studies
EDAT- 1999/09/11 00:00
MHDA- 1999/09/11 00:01
CRDT- 1999/09/11 00:00
PHST- 1999/09/11 00:00 [pubmed]
PHST- 1999/09/11 00:01 [medline]
PHST- 1999/09/11 00:00 [entrez]
AID - 10.1002/1531-8249(199909)46:3<391::aid-ana15>3.0.co;2-0 [doi]
PST - ppublish
SO  - Ann Neurol. 1999 Sep;46(3):391-8. doi: 
      10.1002/1531-8249(199909)46:3<391::aid-ana15>3.0.co;2-0.