The Dynamics and Role of Neutrophils in an Elastase Model of Emphysema
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Date
2014-04-25
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Johns Hopkins University
Abstract
Neutrophils are often early responders to pulmonary damage, rapidly infiltrating the lungs to promote tissue repair following exposure to harmful stimuli. A single dose of intratracheally (IT)-administered elastase results in acute inflammation and progressive emphysematous damage that is also accompanied by a transient and robust neutrophil influx. However, the importance of this early neutrophil recruitment in the chronic progression of emphysema is not well understood. This work seeks to better define the dynamics of pulmonary neutrophil migration in the elastase model of emphysema and to address the hypothesis that the early influx of neutrophils into the lungs contributes to the resolution of acute elastase-mediated injury and affords protection to the lungs from the progressive alveolar destruction that is associated with emphysema.
Bronchoalveolar lavage (BAL) samples were examined by light microscopy at acute time points post-porcine pancreatic elastase administration (post-PPE) to map the cellular response to three enzymatic units of IT elastase in neutrophil-intact BALB/c mice. Systemic depletion of neutrophils was accomplished using a single 500 μg dose of anti-mouse Ly-6G antibody (clone 1A8) injected intraperitoneally (IP) 24 hours prior to elastase treatment. BAL cell counts, total lung capacity (TLC), diffusion factor for carbon monoxide (DFCO), and mean airspace chord lengths (Lm) were each evaluated for effects of neutrophil depletion.
Neutrophils in BAL fluid from control animals were found to peak approximately 24 hours post-PPE before returning to baseline by 72 hours. Treatment with 1A8 resulted in sustained depletion of neutrophils for approximately 5 days that, as expected, ablated the early influx of neutrophils following PPE administration. Neutrophil-depleted mice were found to have no significant exacerbation of emphysematous damage post-PPE. These results do not support the hypothesis that neutrophils contribute to the resolution of lung injury.
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Keywords
Emphysema, Neutrophil