Expression of pro- and anti-apoptosis gene products in brains from paediatric patients with HIV-1 encephalitis

S. Krajewski, H. J. James, J. Ross, B. M. Blumberg, L. G. Epstein, H. E. Gendelman, S. Gummuluru, S. Dewhurst, L. R. Sharer, J. C. Reed, H. A. Gelbard

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

We have previously demonstrated the presence of DNA fragmentation in neurons, macrophages and microglia consistent with apoptosis, but not in reactive astrocytes in brain tissue from paediatric patients with HIV-1 encephalitis (HIVE). To further understand the underlying mechanism(s) for these findings as they relate to gene-directed neural cell death, we studied the in-situ expression of the Bcl-2 family of proteins, including the pro-apoptosis gene product Bax, the anti-apoptosis gene product Bcl-2, and Bcl-x. We demonstrate significantly elevated numbers of Bax-positive microglia and macrophages immunoreactive in basal ganglia and cerebral cortex of children who had HIVE, in comparison to HIV-1 infected children without encephalitis or children who were seronegative for HIV-1. In contrast, patients with HIVE, but not HIV-1 without encephalitis, or seronegative controls, had increased expression of Bcl-2 and Bcl-x in reactive astrocytes in cortex and basal ganglia. In vitro studies using Western blot analysis demonstrated an up-regulation in the levels of Bax, and phosphorylated (i.e. inactive) Bcl-2 in HIV-1 infected macrophages, and in LPS-activated macrophages, relative to levels in virus-negative unstimulated macrophages. These results suggest that productive HIV-1 infection, or cellular activation, renders macrophages more vulnerable to apoptosis. Taken together, these findings suggest that brainresident macrophages and microglia in patients with HIV-1 encephalitis are more prone to undergo apoptosis and that astrocytes in contrast may be resistant to apoptosis. This may represent a mechanism to limit microglial activation and the spread of productive HIV-1 infection in the CNS of children with HIV-1 encephalitis.

Original languageEnglish (US)
Pages (from-to)242-253
Number of pages12
JournalNeuropathology and Applied Neurobiology
Volume23
Issue number3
DOIs
StatePublished - 1997

Keywords

  • Apoptosis
  • Astrocyte
  • Bax
  • Bcl-2
  • Bcl-x
  • CNS
  • Human immunodeficiency virus type 1 (HIV-1)
  • Macrophage
  • Microglia
  • Programmed cell death

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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    Krajewski, S., James, H. J., Ross, J., Blumberg, B. M., Epstein, L. G., Gendelman, H. E., Gummuluru, S., Dewhurst, S., Sharer, L. R., Reed, J. C., & Gelbard, H. A. (1997). Expression of pro- and anti-apoptosis gene products in brains from paediatric patients with HIV-1 encephalitis. Neuropathology and Applied Neurobiology, 23(3), 242-253. https://doi.org/10.1111/j.1365-2990.1997.tb01208.x