Macrophage secretome from women with HIV-associated neurocognitive disorders

Krystal Colon, Juliana Perez-Laspiur, Raymond Quiles, Yolanda Rodriguez, Valerie Wojna, Scott A. Shaffer, John Leszyk, Richard L. Skolasky, Loyda M. Melendez

Research output: Contribution to journalArticle

Abstract

Purpose: Thirty to 50% of HIV patients develop HIV-associated neurocognitive disorders (HANDs) despite combined antiretroviral therapy. HIV-1-infected macrophages release viral and cellular proteins that induce neuronal degeneration and death. We hypothesize that changes in the macrophage secretome of HIV-1 seropositive patients with HAND may dissect proteins related to neurotoxicity. Experimental design: Monocyte-derived macrophages (MDMs) were isolated from the peripheral blood of 12 HIV+ and four HIV- women characterized for neurocognitive function. Serum-free MDM supernatants were collected for protein isolation and quantification with iTRAQ® labeling. Protein identification was performed using a LTQ Orbitrap Velos mass spectrometer and validated in MDM supernatants and in plasma using ELISA. Results: Three proteins were different between normal cognition (NC) and asymptomatic neurocognitive disorders (ANI), six between NC and HIV-associated dementia (HAD), and six between NC and HAD. Among these, S100A9 was decreased in plasma from patients with ANI, and metalloproteinase 9 was decreased in the plasma of all HIV+ patients regardless of cognitive status, and was significantly reduced in supernatant of MDM isolated from patients with ANI. Conclusions and clinical relevance: S100A9 and metalloproteinase 9 have been associated with inflammation and cognitive impairment, and therefore represent potential targets for HAND treatment.

Original languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalProteomics - Clinical Applications
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2016

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Keywords

  • HAND
  • ITRAQ
  • MMP9
  • S100A9
  • Secretome

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Colon, K., Perez-Laspiur, J., Quiles, R., Rodriguez, Y., Wojna, V., Shaffer, S. A., Leszyk, J., Skolasky, R. L., & Melendez, L. M. (2016). Macrophage secretome from women with HIV-associated neurocognitive disorders. Proteomics - Clinical Applications, 10(2), 136-143. https://doi.org/10.1002/prca.201400203