A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis

Yuri Persidsky, Monique Stins, Dennis Way, Marlys H. Witte, Martin Weinand, Kwang Sik Kim, Paul Bock, Howard Eliot Gendelman, Milan Fiala

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

HIV-1 invades the central nervous system early during viral infection, but neurologic impairment usually occurs years later. The strongest predictor for clinical dementia is the absolute numbers of immunocompetent brain macrophages. Thus, how monocytes penetrate the brain during disease remains critical for understanding the neuropathogenic mechanisms of HIV-1 encephalitis. To these ends, we constructed an artificial blood-brain barrier (BBB) consisting of a matrix-coated membrane with brain microvascular endothelial cells (BMVEC) on one side and astrocytes on the other. Astrocyte endfeet contacted the monolayer of BMVEC that formed tight junctions. To determine the role of viral and immune factors in monocyte penetration across the BBB, HIV-infected or uninfected monocytes with or without immune stimulation were placed onto the upper chamber of the BBB model system. Placement of immune-stimulated (LPS-treated) cells onto the BBB construct elicited gaps between BMVEC, with bulging of nuclear zones and increased numbers of vesicular Golgi complexes and endoplasmic reticulum. This correlated with a profound increase (up to 20-fold) in the number of migrating cells. Viral infection did not enhance monocyte migration. The activated monocytes showed increased numbers of philopodia, lysosomes, and vesicular Golgi complexes and expressed large levels of proinflammatory cytokines (TNF-α, IL-6, and IL-10). These data suggest that a major mechanism for the transendothelial migration of monocytes during HIV encephalitis is the immune activation that accompanies viral infection of the central nervous system.

Original languageEnglish (US)
Pages (from-to)3499-3510
Number of pages12
JournalJournal of Immunology
Volume158
Issue number7
StatePublished - Apr 1 1997

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Encephalitis
Blood-Brain Barrier
HIV-1
Monocytes
Endothelial Cells
Brain
Golgi Apparatus
Virus Diseases
Astrocytes
Central Nervous System Viral Diseases
HIV
Transendothelial and Transepithelial Migration
Blood Substitutes
Tight Junctions
Immunologic Factors
Brain Diseases
Lysosomes
Endoplasmic Reticulum
Interleukin-10
Nervous System

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Persidsky, Y., Stins, M., Way, D., Witte, M. H., Weinand, M., Kim, K. S., ... Fiala, M. (1997). A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis. Journal of Immunology, 158(7), 3499-3510.

A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis. / Persidsky, Yuri; Stins, Monique; Way, Dennis; Witte, Marlys H.; Weinand, Martin; Kim, Kwang Sik; Bock, Paul; Gendelman, Howard Eliot; Fiala, Milan.

In: Journal of Immunology, Vol. 158, No. 7, 01.04.1997, p. 3499-3510.

Research output: Contribution to journalArticle

Persidsky, Y, Stins, M, Way, D, Witte, MH, Weinand, M, Kim, KS, Bock, P, Gendelman, HE & Fiala, M 1997, 'A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis', Journal of Immunology, vol. 158, no. 7, pp. 3499-3510.
Persidsky Y, Stins M, Way D, Witte MH, Weinand M, Kim KS et al. A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis. Journal of Immunology. 1997 Apr 1;158(7):3499-3510.
Persidsky, Yuri ; Stins, Monique ; Way, Dennis ; Witte, Marlys H. ; Weinand, Martin ; Kim, Kwang Sik ; Bock, Paul ; Gendelman, Howard Eliot ; Fiala, Milan. / A Model for Monocyte Migration Through the Blood-Brain Barrier during HIV-1 Encephalitis. In: Journal of Immunology. 1997 ; Vol. 158, No. 7. pp. 3499-3510.
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