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Mononuclear phagocytes mediate blood‐brain barrier compromise and neuronal injury during HIV‐1‐associated dementia
Author(s) -
Persidsky Yuri,
Zheng Jialin,
Miller Donald,
Gendelman Howard E.
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.68.3.413
Subject(s) - chemokine , biology , microglia , blood–brain barrier , immune system , immunology , neuroinflammation , stromal cell , central nervous system , inflammation , neuroscience , cancer research
The neuropathogenesis of HIV‐1 infection revolves around the production of secretory factors from immune‐activated brain mononuclear phagocytes (MP). MP‐secreted chemokines may play several roles in HIV‐1 encephalitis (HIVE). These can promote macrophage brain infiltration, blood‐brain barrier (BBB) and neuronal dysfunction during HIV‐1‐associated dementia. We investigate how HIV‐1‐infected MP regulates the production of chemokines and how they influence HIV‐1 neuropathogenesis. We demonstrate that HIV‐1‐infected and immune‐activated MP (for example, microglia) and astrocytes produce β‐chemokines in abundance, as shown in both laboratory assays and within infected brain tissue. HIV‐1‐infected microglia significantly modulate monocyte migration in a BBB model system and in brains of SCID mice with HIVE. HIV‐1‐infected MP down‐regulate tight junction protein and special polarized transport systems on brain microvascular endothelial cells as shown in human autopsy brain tissue and in SCID mice with HIVE. Chemokines can damage neurons directly. Toxicity caused by binding of stromal‐derived factor‐1α to its receptor on neurons exemplifies such mechanism. In toto , these works underscore the diverse roles of chemokines in HIV‐1 neuropathogenesis and lay the foundation for future therapeutic interventions.