Increased activity of matrix metalloproteinases in the cerebrospinal fluid of patients with HIV-associated neurological diseases.
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.
Liuzzi
G M
GM
Department of Biochemistry and Molecular Biology, University of Bari, 70126 Bari, Italy.
Mastroianni
C M
CM
Santacroce
M P
MP
Fanelli
M
M
D'Agostino
C
C
Vullo
V
V
Riccio
P
P
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000201:enzymology; D017088:AIDS-Related Opportunistic Infections / Q000134:cerebrospinal fluid* / Q000201:enzymology; D000293:Adolescent; D000328:Adult; D001812:Blood-Brain Barrier; D018791:CD4 Lymphocyte Count; D002452:Cell Count; D002465:Cell Movement; D002555:Cerebrospinal Fluid / Q000166:cytology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000134:cerebrospinal fluid / Q000201:enzymology; D018450:Disease Progression; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid / Q000201:enzymology; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000201:enzymology; D018023:HIV Seronegativity; D015497:HIV-1; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000134:cerebrospinal fluid* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000134:cerebrospinal fluid* / Q000235:genetics; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000201:enzymology; D016919:Meningitis, Cryptococcal / Q000134:cerebrospinal fluid / Q000201:enzymology; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000134:cerebrospinal fluid / Q000201:enzymology; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000201:enzymology; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000201:enzymology; D016781:Toxoplasmosis, Cerebral / Q000134:cerebrospinal fluid / Q000201:enzymology; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000201:enzymology
D002556:Cerebrospinal Fluid Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9