title: Macrophage secretome from women with HIV-associated neurocognitive disorders.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  S100A9 and metalloproteinase 9 have been associated with inflammation and cognitive impairment, and therefore represent potential targets for HAND treatment.
authors.affiliation: Department of Microbiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Krystal
authors.initials: K
authors.lastname: Colon
authors.affiliation: RCMI Translational Proteomics Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Perez-Laspiur
authors.affiliation: Metropolitan Campus, Interamerican University, San Juan, PR, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Quiles
authors.affiliation: Department of Microbiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Rodriguez
authors.affiliation: Division of Neurology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Wojna
authors.affiliation: Proteomics and Mass Spectrometry Facility, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Shaffer
authors.affiliation: Proteomics and Mass Spectrometry Facility, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Leszyk
authors.affiliation: Department of Orthopaedic Surgery, John Hopkins University, Baltimore, MD, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Skolasky
authors.affiliation: Department of Microbiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.|RCMI Translational Proteomics Center, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Loyda M
authors.initials: LM
authors.lastname: Melendez
mesh_terms: D015526:AIDS Dementia Complex / Q000150:complications* / Q000821:virology; D040502:Calgranulin B / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D019965:Neurocognitive Disorders / Q000150:complications* / Q000821:virology; D040901:Proteomics
chemical_list: D040502:Calgranulin B; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: HAND; MMP9; S100A9; Secretome; iTRAQ