The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations.

Authors:
Paola Cinque
Paola Cinque
San Raffaele Scientific Institute
Italy
Manuela Nebuloni
Manuela Nebuloni
University of Milan
Italy
Maria Lisa Santovito
Maria Lisa Santovito
San Raffaele Scientific Institute and Hospital
Italy
Richard W Price
Richard W Price
University of California San Francisco
United States
Lars Hagberg
Lars Hagberg
University of Gothenburg
Sweden
Arabella Bestetti
Arabella Bestetti
San Raffaele Scientific Institute
Italy
Gianluca Vago
Gianluca Vago
University of Milan
Italy

Ann Neurol 2004 May;55(5):687-94

Clinic of Infectious Diseases, San Raffaele Scientific Institute, University of Milan, Italy.

The urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play an important role in extracellular matrix degradation and cell migration in the central nervous system (CNS). To investigate the role of the uPA/uPAR system in the pathophysiology of acquired immunodeficiency syndrome dementia complex (ADC), we measured soluble uPAR (suPAR) levels in cerebrospinal fluid (CSF) and plasma from human immunodeficiency virus (HIV)-1-infected patients and controls. CSF suPAR levels were significantly higher in HIV-1-infected patients than in controls and in patients with ADC or opportunistic CNS infections (CNS-OIs) than in neurologically asymptomatic patients, irrespective of HIV-1 disease stage. The highest levels of suPAR were found in patients with ADC, and among those with CNS-OIs in patients with cytomegalovirus encephalitis or cryptococcosis. Plasma suPAR levels were higher in HIV-1-infected patients than in controls and increased with HIV-1 disease stage regardless of the presence of CNS disease. In patients with ADC or CNS-OIs, CSF suPAR levels correlated with CSF HIV-1 RNA, but not with plasma suPAR concentrations. Highly active antiretroviral therapy was associated with a significant and parallel decrease of both CSF suPAR and HIV-1 RNA. In brain tissue from patients with HIV-1 encephalitis, uPAR was highly expressed by microglial and multinucleated giant cells staining positively for HIV-1. The overexpression of uPAR in the CNS of patients with ADC suggests that the uPA/uPAR system may contribute to the tissue injury and neuronal damage in this disease.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.20076DOI Listing
May 2004
30 Reads

Publication Analysis

Top Keywords

patients adc
16
supar levels
16
patients controls
12
csf supar
12
hiv-1-infected patients
12
patients
10
disease stage
8
hiv-1 disease
8
adc cns-ois
8
upa/upar system
8
higher hiv-1-infected
8
hiv-1 rna
8
dementia complex
8
levels higher
8
plasma supar
8
supar
7
hiv-1
6
levels
5
adc
5
csf
5

References

(Supplied by CrossRef)
Article in J Neurovirol
Nottet et al.
J Neurovirol 1999
Article in J Biol Chem
Ellis et al.
J Biol Chem 1991
Article in Nat Rev Mol Cell Biol
Blasi et al.
Nat Rev Mol Cell Biol 2002
Article in Science
Wei et al.
Science 1996
Article in Proc Natl Acad Sci USA
Resnati et al.
Proc Natl Acad Sci USA 2002
Article in J Biol Chem
Wei et al.
J Biol Chem 1994
Article in Neurology
Neurology 1991
Article in MMWR Recomm Rep
MMWR Recomm Rep 1992
Article in J Natl Cancer Inst
Stephens et al.
J Natl Cancer Inst 1999
Article in Blood
Sidenius et al.
Blood 2000
Article in Brain Pathol
Budka et al.
Brain Pathol 1991

Similar Publications