Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

Abstract

Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in increased bronchoalveolar lavage fluid neutrophils and macrophages after single and repetitive exposures. Lavage fluid TNF␣, IL-6, keratinocyte chemoattractant, and macrophage inflammatory protein-2 were significantly increased after single and repetitive dust exposures, but were dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure induced PKC␣ and -ε activation in isolated tracheal epithelial cells but were dampened with repetitive exposures. Ex vivo stimulation of alveolar macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and phagocytic ability. Significant lung pathology occurred with development of mixed mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after repetitive dust exposure, a novel observation. Airway hyperresponsiveness to methacholine occurred after single dust exposure but resolved after 2 wk. Collectively, intranasal exposure to DE results in significant lung inflammatory and pathological responses marked by a modulated innate immune response to single and repetitive dust exposures that is associated with PKC activity.

Moringa Tea Blocks Acute Lung Inflammation Induced by Swine Confinement Dust Through a Mechanism Involving TNF-α Expression, C-Jun N-Terminal Kinase Activation and Neutrophil Regulation

“…Inhalation of endotoxins and carbon dioxide at levels above the recommended health threshold limits (Mc Donnell et al, 2008) can lead to acute and chronic airway inflammation (Schierl et al, 2007). Poole et al (2009) reported increased cellular inflammation, predominated by neutrophils, in mouse BALF following a single intranasal instillation of DE.…”

“…In humans and animals, lung challenge with Lipopolysaccharide (LPS) causes a neutrophil-rich inflammatory responses and intranasal instillation of swine confinement dust extracts in mice has been shown to lead to increased cellular inflammation that is predominated by neutrophils (Sandström et al, 1994) (Jagielo et al, 1996;Poole et al, 2009). Differential cell analysis of the cells collected from the BAL show that neutrophils were the predominant cell type detected in the in the lungs 24 h after LPS and 10% DE challenge (Fig.…”

Exposure to Swine Housing Dust Modulates Macrophage Morphology and Function

“…Airway inflammation can lead to loss of lung function, as measured by the decrease in forced expiratory air in one second or less (Costa et al, 2007). Poole et al (2009b) reported increased cellular inflammation, predominated by neutrophils and neutrophils and macrophages, in mouse BALF following a single and 1/2 week intranasal instillation of DE, respectively. Mice continuously exposed to swine CAFO dust via nebulizer for 4 h developed BALFneutrophilia (Mueller-Anneling et al, 2006).…”

“…The dust extract was prepared using a protocol similar to Poole et al (2009b). Briefly, several grams of settled dust from raised surfaces were collected from the gestation and farrowing rooms at North Carolina A and T State University's Swine Research Unit and brushed into a zip top bag.…”

Popcorn Flavoring Effects on Reactivity of Rat Airways in Vivo and in Vitro

“…A major purpose of the investigation was to compare and contrast the effects of diacetyl and 2,3-pentanedione in airways in vivo and in vitro. In the first series of experiments, alterations were determined in respiratory mechanics, that is, lung resistance and dynamic compliance (R L and C dyn , respectively), as well as reactivity to inhaled MCh, following diacetyl or 2,3-pentanedione inhalation (Poole et al, 2009;Yao et al, 2010). It was of interest to identify the concentration range over which diacetyl and 2,3-pentanedione may produce such effects.…”