Diminished matrix metalloproteinase 9 secretion in human immunodeficiency virus-infected mononuclear phagocytes

Modulation of innate immunity and implications for neurological disease

Pawel S Ciborowski, Yoshimi Enose, Andrea MacK, Melissa Fladseth, Howard Eliot Gendelman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neurotoxic secretory products from virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) orchestrate the neuropathogenesis of human immunodeficiency virus type one (HIV-1) infection. To uncover such MP products and their relationship to disease, we used a proteomics platform consisting of one dimensional polyacrylamide gel electrophoresis (1-DE), mass spectrometry peptide sequencing, and bioinformatics in order to identify from HIV-1-infected monocyte-derived macrophages (MDM) secretions. Matrix metalloproteinase 9 (MMP 9) secreted in abundance in MDM was markedly down-regulated following viral infection. A negative correlation between MMP 9 and HIV-1 reverse transcriptase activity was shown by quantitative Western blot assays. These data further demonstrate immunoregulatory activities of HIV-1-infected MDM providing unique insights into cellular function in disease.

Original languageEnglish (US)
Pages (from-to)11-16
Number of pages6
JournalJournal of Neuroimmunology
Volume157
Issue number1-2 SPEC. ISS.
DOIs
StatePublished - Dec 1 2004

Fingerprint

Matrix Metalloproteinase 9
Phagocytes
Innate Immunity
Macrophages
HIV
HIV-1
Microglia
Virus Diseases
Computational Biology
Proteomics
HIV Infections
Polyacrylamide Gel Electrophoresis
Mass Spectrometry
Western Blotting
Viruses
Peptides

Keywords

  • HIV-1-associated dementia
  • Human immunodeficiency virus
  • Matrix metalloproteinases
  • Monocyte-derived macrophages
  • Proteomics

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

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abstract = "Neurotoxic secretory products from virus-infected mononuclear phagocytes (MP; perivascular macrophages and microglia) orchestrate the neuropathogenesis of human immunodeficiency virus type one (HIV-1) infection. To uncover such MP products and their relationship to disease, we used a proteomics platform consisting of one dimensional polyacrylamide gel electrophoresis (1-DE), mass spectrometry peptide sequencing, and bioinformatics in order to identify from HIV-1-infected monocyte-derived macrophages (MDM) secretions. Matrix metalloproteinase 9 (MMP 9) secreted in abundance in MDM was markedly down-regulated following viral infection. A negative correlation between MMP 9 and HIV-1 reverse transcriptase activity was shown by quantitative Western blot assays. These data further demonstrate immunoregulatory activities of HIV-1-infected MDM providing unique insights into cellular function in disease.",
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AU - MacK, Andrea

AU - Fladseth, Melissa

AU - Gendelman, Howard Eliot

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