HIV-1 infected monocyte-derived macrophages affect the human brain microvascular endothelial cell proteome: New insights into blood-brain barrier dysfunction for HIV-1-associated dementia

Mary Ricardo-Dukelow, Irena Kadiu, Wojciech Rozek, Joshua Schlautman, Yuri Persidsky, Pawel Ciborowski, Georgette D. Kanmogne, Howard E. Gendelman

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Blood-brain barrier (BBB) compromise and transendothelial migration of HIV-infected leukocytes into the central nervous system (CNS) underlies the neuropathogenesis of HIV-1 infection. How this occurs is incompletely understood. We used a proteomic platform integrating difference gel electrophoresis and tandem mass spectrometry peptide sequencing to determine the effects that HIV-1-infected macrophages have on human brain microvascular endothelial cell (HBMEC) protein profiles. HIV-1 infected monocyte-derived macrophages (MDM) induced the upregulation of over 200 HBMEC proteins. These included metabolic, voltage-gated ion channels, heat shock, transport, cytoskeletal, regulatory, and calcium binding proteins. Results were validated by Western blot analysis. We conclude that HIV-1-infected MDM affect the HBMEC proteome and, in this way, affect BBB dysfunction and the development of HIV-1 CNS disease.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalJournal of Neuroimmunology
Volume185
Issue number1-2
DOIs
StatePublished - Apr 2007

Keywords

  • 2D difference gel electrophoresis
  • Human brain microvascular endothelial cells
  • Human immunodeficiency virus
  • Monocyte-derived macrophages
  • Proteomics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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