title: The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations.
abstract: 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.
authors.affiliation: Clinic of Infectious Diseases, San Raffaele Scientific Institute, University of Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Maria Lisa
authors.initials: ML
authors.lastname: Santovito
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslen
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
authors.forename: Arabella
authors.initials: A
authors.lastname: Bestetti
authors.forename: Gianluca
authors.initials: G
authors.lastname: Vago
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Nicolai
authors.initials: N
authors.lastname: Sidenius
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015497:HIV-1; D006801:Humans; D008137:Longitudinal Studies; D009422:Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000097:blood; D055293:Receptors, Urokinase Plasminogen Activator; D018709:Statistics, Nonparametric; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator