Mononuclear phagocyte differentiation, activation, and viral infection regulate matrix metalloproteinase expression: implications for human immunodeficiency virus type 1-associated dementia
| Autor: | Raisa N. Persidskaia, Anuja Ghorpade, Yuri Persidsky, Myhanh Che, Howard E. Gendelman, Xiao Juan Liu, Radhika Suryadevara |
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| Rok vydání: | 2001 |
| Předmět: |
Leukocyte migration
AIDS Dementia Complex Cellular differentiation Immunology Matrix metalloproteinase Microbiology Fetus Virology medicine Humans Cells Cultured Phagocytes CD40 biology Microglia Monocyte Brain Cell Differentiation Mononuclear phagocyte system Immunohistochemistry Matrix Metalloproteinases Cell biology medicine.anatomical_structure Insect Science biology.protein Leukocytes Mononuclear Pathogenesis and Immunity Cell activation |
| Zdroj: | Journal of virology. 75(14) |
| ISSN: | 0022-538X |
| Popis: | The pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is mediated mainly by mononuclear phagocyte (MP) secretory products and their interactions with neural cells. Viral infection and MP immune activation may affect leukocyte entry into the brain. One factor that influences central nervous system (CNS) monocyte migration is matrix metalloproteinases (MMPs). In the CNS, MMPs are synthesized by resident glial cells and affect the integrity of the neuropil extracellular matrix (ECM). To ascertain how MMPs influence HAD pathogenesis, we studied their secretion following MP differentiation, viral infection, and cellular activation. HIV-1-infected and/or immune-activated monocyte-derived macrophages (MDM) and human fetal microglia were examined for production of MMP-1, -2, -3, and -9. MMP expression increased significantly with MP differentiation. Microglia secreted high levels of MMPs de novo that were further elevated following CD40 ligand-mediated cell activation. Surprisingly, HIV-1 infection of MDM led to the down-regulation of MMP-9. In encephalitic brain tissue, MMPs were expressed within perivascular and parenchymal MP, multinucleated giant cells, and microglial nodules. These data suggest that MMP production in MP is dependent on cell type, differentiation, activation, and/or viral infection. Regulation of MMP expression by these factors may contribute to neuropil ECM degradation and leukocyte migration during HAD. |
| Databáze: | OpenAIRE |
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