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Sousa L.P.,Programa de Pos Graduacao em Biologia Celular | Sousa L.P.,Laboratorio Of Imunofarmacologia | Sousa L.P.,Federal University of Minas Gerais | Vago J.P.,Programa de Pos Graduacao em Biologia Celular | And 11 more authors.
Journal of Leukocyte Biology | Year: 2012

This study aimed at assessing whether AnxA1, a downstream mediator for the anti-inflammatory effects of GCs, could affect the fate of immune cells in tissue exudates, using LPS-induced pleurisy in BALB/c mice. AnxA1 protein expression in exudates was increased during natural resolution, as seen at 48-72 h post-LPS, an effect augmented by treatment with GC and associated with marked presence of apoptotic neutrophils in the pleural exudates. The functional relevance of AnxA1 was determined using a neutralizing antibody or a nonspecific antagonist at FPR/ALXRs: either treatment inhibited both spontaneous and GC-induced resolution of inflammation. Injection of Ac2-26 (100 μg, given 4 h into the LPS response), an AnxA1-active N-terminal peptide, promoted active resolution and augmented the extent of neutrophil apoptosis. Such an effect was prevented by the pan-caspase inhibitor zVAD-fmk. Mechanistically, resolution of neutrophilic inflammation was linked to cell apoptosis with activation of Bax and caspase-3 and inhibition of survival pathways Mcl-1, ERK1/2, and NF-κB. These novel in vivo data, using a dynamic model of acute inflammation, provide evidence that AnxA1 is a mediator of natural and GC-induced resolution of inflammation with profound effects on neutrophil apoptosis. © Society for Leukocyte Biology. Source


Simon D.,Programa de Pos Graduacao em Biologia Celular | Simon D.,Laboratorio Of Biomarcadores Do Trauma | Nicol J.M.B.,Programa de Pos Graduacao em Biologia Celular | Sabino Da Silva S.,Laboratorio Of Biomarcadores Do Trauma | And 10 more authors.
Brain Injury | Year: 2015

Objectives: Severe traumatic brain injury (TBI) is associated with a 30-70% mortality rate. Nevertheless, in clinical practice there are no effective biomarkers for the prediction of fatal outcome following severe TBI. Therefore, the aim was to determine whether ferritin serum levels are associated with ICU mortality in patients with severe TBI. Methods: This prospective study enrolled 69 male patients who suffered severe TBI [Glasgow Coma Scale (GCS) 3-8 at emergency room admission]. The serum ferritin protein level was determined at ICU admission (mean 5.6±2.5 hours after emergency room admission). Results: Severe TBI was associated with a 39% mortality rate. Higher serum ferritin concentrations were significantly associated with lower hospital admission GCS scores (p=0.049). Further, there was a significant association between higher ferritin concentrations and fatal outcome (289.5±27.1gL-1 for survivors and 376.5±31.5gL-1 for non-survivors, respectively, mean±SEM, p=0.032). Conclusions: Increased serum ferritin levels were associated with lower hospital admission GCS scores and predicted short-term fatal outcome following severe TBI. © 2015 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted. Source

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