Proteomics. Clinical applications · 2015
Macrophage secretome from women with HIV-associated neurocognitive disorders.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Colon Krystal, Perez-Laspiur Juliana, Quiles Raymond, Rodriguez Yolanda, Wojna Valerie, Shaffer Scott A, Leszyk John, Skolasky Richard L, Melendez Loyda M
Аннотация
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.
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.