Mechanisms of leukocyte trafficking into the CNS

Dona T. Wu, Scott E. Woodman, Jonathan M. Weiss, Carrie M. McManus, Teresa G. D'Aversa, Joseph Hesselgesser, Eugene O. Major, Avi Nath, Joan W. Berman

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

HIV-1 encephalitis occurs in up to one-third of HIV-1-infected individuals. The mechanisms through which this pathology develops are thought to involve viral passage across the blood-brain barrier (BBB), as well as entry of HIV-infected and/or uninfected inflammatory cells into the central nervous system (CNS). Viral proteins and cytokines may also contribute to the pathogenesis of encephalitis. We show that the chemokines SDF-1 and MCP-1 induce transmigration of uninfected human lymphocytes and monocytes across our model of the BBB, a co-culture of human fetal astrocytes and endothelial cells. We also demonstrate that the HIV-1 protein Tat induces adhesion molecule expression and chemokine production by human fetal astrocytes and microglia, which could further contribute to leukocyte entry into the CNS. Finally, our data indicate that inflammatory cytokines modulate the expression of CXCR4, a co-receptor for HIV-1, on human fetal astrocytes, suggesting that these cytokines may potentially modulate the infectability of astrocytes by HIV-1. These findings support the hypothesis that there may be several different mechanisms that contribute to the development and progression of HIV-1 encephalitis.

Original languageEnglish (US)
JournalJournal of NeuroVirology
Volume6
Issue numberSUPPL. 1
StatePublished - 2000

Fingerprint

HIV-1
Leukocytes
Central Nervous System
Astrocytes
Encephalitis
Cytokines
Blood-Brain Barrier
Chemokines
Human Immunodeficiency Virus Proteins
Microglia
Viral Proteins
Coculture Techniques
Monocytes
Endothelial Cells
HIV
Lymphocytes
Pathology

Keywords

  • Adhesion molecules
  • Blood-brain barrier
  • Chemokines
  • CXCR4
  • Leukocyte transmigration
  • Tat

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Wu, D. T., Woodman, S. E., Weiss, J. M., McManus, C. M., D'Aversa, T. G., Hesselgesser, J., ... Berman, J. W. (2000). Mechanisms of leukocyte trafficking into the CNS. Journal of NeuroVirology, 6(SUPPL. 1).

Mechanisms of leukocyte trafficking into the CNS. / Wu, Dona T.; Woodman, Scott E.; Weiss, Jonathan M.; McManus, Carrie M.; D'Aversa, Teresa G.; Hesselgesser, Joseph; Major, Eugene O.; Nath, Avi; Berman, Joan W.

In: Journal of NeuroVirology, Vol. 6, No. SUPPL. 1, 2000.

Research output: Contribution to journalArticle

Wu, DT, Woodman, SE, Weiss, JM, McManus, CM, D'Aversa, TG, Hesselgesser, J, Major, EO, Nath, A & Berman, JW 2000, 'Mechanisms of leukocyte trafficking into the CNS', Journal of NeuroVirology, vol. 6, no. SUPPL. 1.
Wu DT, Woodman SE, Weiss JM, McManus CM, D'Aversa TG, Hesselgesser J et al. Mechanisms of leukocyte trafficking into the CNS. Journal of NeuroVirology. 2000;6(SUPPL. 1).
Wu, Dona T. ; Woodman, Scott E. ; Weiss, Jonathan M. ; McManus, Carrie M. ; D'Aversa, Teresa G. ; Hesselgesser, Joseph ; Major, Eugene O. ; Nath, Avi ; Berman, Joan W. / Mechanisms of leukocyte trafficking into the CNS. In: Journal of NeuroVirology. 2000 ; Vol. 6, No. SUPPL. 1.
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