Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia

Y. Persidsky, Jialin C Zheng, D. Miller, Howard Eliot Gendelman

Research output: Contribution to journalReview article

126 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalJournal of Leukocyte Biology
Volume68
Issue number3
StatePublished - Dec 27 2000

Fingerprint

Phagocytes
Blood-Brain Barrier
Dementia
HIV-1
Wounds and Injuries
Chemokines
Brain
Encephalitis
SCID Mice
Microglia
Tight Junction Proteins
Neurons
Immunologic Factors
Astrocytes
HIV Infections
Monocytes
Autopsy
Down-Regulation
Endothelial Cells
Macrophages

Keywords

  • Astrocyte
  • Chemokine
  • Chemokine receptor
  • Endothelial cell
  • Microglia
  • Tight junction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this

Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. / Persidsky, Y.; Zheng, Jialin C; Miller, D.; Gendelman, Howard Eliot.

In: Journal of Leukocyte Biology, Vol. 68, No. 3, 27.12.2000, p. 413-422.

Research output: Contribution to journalReview article

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