An analysis of HIV-1-associated inflammatory products in brain tissue of humans and SCID mice with HIV-1 encephalitis
| Autor: | Manuel Buttini, Howard E. Gendelman, Paul J. Bock, Jenae Limoges, Yuri Persidsky |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male AIDS Dementia Complex viruses Human immunodeficiency virus (HIV) Vascular Cell Adhesion Molecule-1 HIV Infections Brain tissue Mice SCID Scid mice Biology medicine.disease_cause Polymerase Chain Reaction Cellular and Molecular Neuroscience Immunocompromised Host Mice Hiv 1 encephalitis Animal model Virology HIV encephalitis medicine Dementia Animals Humans Encephalitis Viral Child Aged Brain Chemistry Neurons Macrophages Brain Middle Aged medicine.disease Intercellular Adhesion Molecule-1 body regions Neurology Viral replication Immunology HIV-1 Cytokines Female Severe Combined Immunodeficiency Neurology (clinical) |
| Zdroj: | Journal of neurovirology. 3(6) |
| ISSN: | 1355-0284 |
| Popis: | The human immunodeficiency virus type 1 (HIV)-associated dementia complex (ADC) is a neuroimmunological disorder fueled by viral replication in mononuclear phagocytes (MP) (brain macrophages and microglia). The elucidation of MP inflammatory factors involved in neurological dysfunction is pivotal for unraveling pathogenic mechanisms and in developing new therapies for this disease. Recent advances in animal model systems for ADC and its associated encephalitis have provided important insights into how virus-infected macrophages cause brain injury. Indeed, the stereotactic inoculation of HIV infected monocytes into the basal ganglia/cortex of mice with severe combined immunodeficiency disease (SCID) results in pathological features similar to those of human HIV-1 encephalitis (HIVE). We used this SCID model to study the roles of macrophage secretory factors in HIVE. The expression of interleukin-1 (IL-1 beta, IL-6, IL-10), tumor necrosis factors-alpha (TNF alpha), vascular endothelial growth factor (VEGF), and adhesion molecules (E-selectin, intracellular cell adhesion molecule (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1)) in encephalitic brains of mice and humans was evaluated by semi-quantitative polymerase chain reaction (PCR). In SCID mice with HIVE, human and mouse TNF alpha, and mouse IL-6, VEGF, VCAM-1 and E-selectin were expressed at high levels. These results paralleled, to a great extent, those in HIVE brain tissues. Laser scanning confocal microscopy performed to assess the associated neuronal damage showed that microtubule associated protein-2 (MAP-2) immunoreactive dendrites were significantly reduced in both the ipsilateral and contralateral hemispheres of encephalitic mice. These results demonstrate the importance of macrophage inflammatory products in the pathogenesis of HIVE and further validates this model of viral encephalitis in SCID mice. |
| Databáze: | OpenAIRE |
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