|Göteborgs universitets publikationer
Expression of the urokinase plasminogen activator and its receptor in HIV-1-associated central nervous system disease.
Författare och institution:
Nicolai Sidenius (-); Manuela Nebuloni (-); Stefania Sala (-); Pietro Zerbi (-); Richard W Price (-); Magnus Gisslén (Institutionen för invärtesmedicin, Avdelningen för infektionssjukdomar); Lars Hagberg (Institutionen för invärtesmedicin, Avdelningen för infektionssjukdomar); Luca Vago (-); Adriano Lazzarin (-); Francesco Blasi (-); Paola Cinque (-)
Journal of neuroimmunology, 157 ( 1-2 ) s. 133-9
Artikel, refereegranskad vetenskaplig
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP
Acquired Immunodeficiency Syndrome, complications, Central Nervous System Diseases, cerebrospinal fluid, etiology, virology, HIV Core Protein p24, metabolism, HIV-1, physiology, Humans, Immunohistochemistry, methods, Receptors, Cell Surface, metabolism, Regression Analysis, Urinary Plasminogen Activator, cerebrospinal fluid