RESUMO
Lung inflammation, caused by acute exposure to ozone (O3) - one of the six criteria air pollutants - is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung and their number increases following O3 exposure. However, the role of AMØs in promoting or limiting O3-induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O3 exposure, lineage tracing, genetic knockouts, and data from O3-exposed human volunteers to define the role and ontogeny of AMØs during acute O3 exposure. Lineage tracing experiments showed that 12, 24, and 72 h after exposure to O3 (2 ppm) for 3h all AMØs were tissue-resident origin. Similarly, in humans exposed to FA and O3 (200 ppb) for 135 minutes, we did not observe ~21h post-exposure an increase in monocyte-derived AMØs by flow cytometry. Highlighting a role for tissue-resident AMØs, we demonstrate that depletion of tissue-resident AMØs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O3 exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMØ demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK - a key receptor involved in efferocytosis - also resulted in impaired clearance of apoptotic neutrophils followed O3 exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O3-induced inflammation via MerTK-mediated efferocytosis.
RESUMO
Introducción. El entrenamiento de la marcha en órtesis robótica ha demostrado buenos resultados en pacientes con lesión medular incompleta (LMI) crónica; la retroalimentación auditiva puede suplir la información dada normalmente por las vías sensitivas afectadas. Objetivo. Evaluar el efecto a corto plazo del entrenamiento de la marcha en órtesis robótica con retroalimentación auditiva en pacientes con LMI crónica. Material y método. Se estudió a 31 pacientes con LMI asignados aleatoriamente a 2 grupos: uno control con entrenamiento únicamente en órtesis robótica y otro experimental con entrenamiento en órtesis robótica y retroalimentación auditiva realizada mediante un metrónomo con frecuencia igual a la de la cadencia. Se midieron las variables espacio temporales de la marcha así como el torque, la espasticidad y los arcos de movilidad en caderas y rodillas antes y después del tratamiento mediante un tapete instrumentado y la órtesis robótica, respectivamente. Se realizaron estudios de varianza, covarianza y correlaciones bivariadas para el análisis de resultados. Resultados. Se encontró mejoría estadísticamente significativa en velocidad y cadencia de la marcha, arcos de movilidad, torque y espasticidad en pacientes del grupo experimental y un cambio favorable y significativo en el uso de ayudas técnicas para la marcha. Conclusiones. El programa propuesto mejoró el patrón de marcha en pacientes con LMI crónica. Se necesita evaluar la persistencia de los cambios a largo plazo así como realizar más estudios con retroalimentación auditiva en otras enfermedades (AU)
ntroduction. Gait training on a robotic orthosis has shown good results in patients with chronic incomplete spinal cord injury (SCI). Auditory feedback in these patients can replace the information normally given by the sensory pathways. Objective. To evaluate the effects of gait training on a robotic orthosis with auditory feedback in patients with chronic SCI. Material and methods. We studied 31 patients with chronic incomplete SCI, who were randomized to 2 groups. Control group was trained on a robotic orthosis and experimental group received auditory feedback added to robotic orthosis training. Auditory feedback consisted on a metronome whose frequency was equal to gait cadence. The variables measured were spatiotemporal gait (by an instrumented mat), torque, spasticity, and range of motion in the hips and knees (by a robotic orthosis) before and after the assigned treatment. Calculation of variance, covariance and bivariate correlation were conducted for the analysis of results. Results. We found a statistically significant improvement in gait speed and cadence, range of motion, torque and spasticity in the experimental group and a positive and significant change in the use of assistive devices for walking. Conclusions. The proposed program improved gait pattern in patients with chronic SCI. Further studies are needed to assess the persistence of these changes in the long-term, as well as the use of auditory feedback in other disorders (AU)
