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Increased activity of matrix metalloproteinases in the cerebrospinal fluid of patients with HIV-associated neurological diseases

J Neurovirol. 2000 Apr;6(2):156-63. doi: 10.3109/13550280009013159.

Abstract

Matrix metalloproteinases (MMPs) have been identified as mediators of brain injury in HIV-associated neurological diseases. The activity of the 72 kDa gelatinase A (MMP-2) and 92 kDa gelatinase B (MMP-9) was detected by zymography in the cerebrospinal fluid (CSF) of 138 HIV-infected patients (40 with AIDS dementia, 83 with brain opportunistic infections and 15 neurologically asymptomatic), 26 HIV-seronegative individuals with inflammatory neurological diseases (IND) and 12 HIV-seronegative subjects with noninflammatory neurological diseases (NIND). MMP-2 was present in all CSF samples from HIV-seropositive and HIV-seronegative individuals, including those of subjects with NIND. On the contrary, MMP-9 was absent in the CSF of NIND controls, whereas the activity of this MMP was found in the 77 - 100% of CSF samples from HIV-infected patients, including those with HIV dementia, central nervous system (CNS) opportunistic infections or neurologically asymptomatic subjects. The highest levels of MMP-9 were found in the CSF of patients with cryptococcosis, cytomegalovirus encephalitis and tuberculous meningitis and were comparable with those found in the CSF of HIV-negative patients with multiple sclerosis or meningitis. A significant correlation between CSF MMP-9 activity and CSF cell count was found only in patients with HIV dementia. The increased CSF activity of MMPs capable to degrade components of the extracellular matrix of blood-brain barrier may contribute to the transendothelial migration of virus-infected cells into the CNS and development of HIV-associated neurologic damage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / cerebrospinal fluid*
  • AIDS Dementia Complex / enzymology
  • AIDS-Related Opportunistic Infections / cerebrospinal fluid*
  • AIDS-Related Opportunistic Infections / enzymology
  • Adolescent
  • Adult
  • Blood-Brain Barrier
  • CD4 Lymphocyte Count
  • Cell Count
  • Cell Movement
  • Cerebrospinal Fluid / cytology
  • Cerebrospinal Fluid Proteins / analysis*
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / cerebrospinal fluid
  • Cytomegalovirus Infections / enzymology
  • Disease Progression
  • Encephalitis, Viral / cerebrospinal fluid
  • Encephalitis, Viral / enzymology
  • Female
  • HIV Infections / cerebrospinal fluid*
  • HIV Infections / enzymology
  • HIV Seronegativity
  • HIV-1*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / cerebrospinal fluid*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / cerebrospinal fluid*
  • Matrix Metalloproteinase 9 / genetics
  • Meningitis, Bacterial / cerebrospinal fluid
  • Meningitis, Bacterial / enzymology
  • Meningitis, Cryptococcal / cerebrospinal fluid
  • Meningitis, Cryptococcal / enzymology
  • Middle Aged
  • Motor Neuron Disease / cerebrospinal fluid
  • Motor Neuron Disease / enzymology
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / enzymology
  • Nervous System Diseases / cerebrospinal fluid*
  • Nervous System Diseases / enzymology
  • Toxoplasmosis, Cerebral / cerebrospinal fluid
  • Toxoplasmosis, Cerebral / enzymology
  • Tuberculosis, Meningeal / cerebrospinal fluid
  • Tuberculosis, Meningeal / enzymology

Substances

  • Cerebrospinal Fluid Proteins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9