title: Expression of the urokinase plasminogen activator and its receptor in HIV-1-associated central nervous system disease.
abstract: The urokinase plasminogen activator (uPA) and its receptor (uPAR) play important physiological functions in extracellular proteolysis, as well as cell adhesion and migration. Through dysregulation of these functions, the uPA/uPAR system might be involved in the pathogenesis of AIDS dementia complex (ADC), and, in fact, uPAR has been found to be overexpressed in the cerebrospinal fluid (CSF) and brain tissues of patients with ADC. On the other hand, its ligand uPA has been shown to down-regulate HIV replication in vitro. In this study, we examined uPAR and uPA expression in the brain of HIV-related lesions, as well as CSF levels of soluble uPAR (suPAR), uPA, and complexes between these two molecules (suPAR/uPA) in patients with HIV infection with or without ADC. uPAR was highly expressed by macrophages in both HIV encephalitis (HIV-E) or leukoencephalopathy (HIV-LE), with a distribution exceeding that of HIV p24 antigen. In contrast, uPA was detected only on rare cells in most of the cases. Both uPA and suPAR/uPA complex concentrations were significantly correlated with CSF suPAR levels, and CSF concentrations of both markers were higher in ADC patients than controls. However, uPA levels were substantially lower than corresponding suPAR levels. Although these findings remain correlative, they add support to the hypothesis that uPAR might be an important participant in the events leading to ADC. Additionally, these findings are consistent with a model in which overexpression of uPAR and overproduction of its soluble form may promote HIV replication via binding and removal of uPA from cell surface.
authors.affiliation: Molecular Genetics Unit, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Sidenius
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Stefania
authors.initials: S
authors.lastname: Sala
authors.forename: Pietro
authors.initials: P
authors.lastname: Zerbi
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: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.forename: Paola
authors.initials: P
authors.lastname: Cinque
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000821:virology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D012044:Regression Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000134:cerebrospinal fluid*
chemical_list: D016655:HIV Core Protein p24; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator