Repeat organic dust exposure–induced monocyte inflammation is associated with protein kinase C activity

Poole, Jill; Wyatt, Todd A.; Essen, Susanna G. Von; Hervert, John; Parks, Conrad; Mathisen, T.; Romberger, Debra J.

doi:10.1016/j.jaci.2007.04.033

Cited by 43 publications

(53 citation statements)

References 29 publications

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“…29 Our findings in this study are also consistent with other studies and our previous studies demonstrating that the endotoxin component in swine barn dust does not completely explain the immune inflammatory response in cultured airway epithelial cells and monocytes. [6][7][8] It appears then that gram positive bacterial components may be the driving component of the organic dust-induced responses observed in our study, but LPS + PGN together most closely mimicked the observations we observed with ODE, suggesting that combinations of biological agents are important in real life exposures. However, it would be an oversimplification to state that a TLR2 and/or TLR4 agonist completely explains the effect observed with organic dust as we did not observe any modulation in TLR2 and TLR4 cell surface expression with organic dust conditioning.…”

Section: Discussionsupporting

confidence: 85%

Repetitive organic dust exposure in vitro impairs macrophage differentiation and function

Poole

Alexis

Parks

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Discussionsupporting

confidence: 85%

Repetitive organic dust exposure in vitro impairs macrophage differentiation and function

Poole

Alexis

Parks

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Measurement of BALF components including immune cells, microbial/host protein content, cytokines and chemokines, is the method of choice for elevating airway and lung inflammation (Elizur et al, 2008;Sagel et al, 2009). This is consistent with findings reported by Poole et al (2007) where acute exposure to dust induces an inflammatory response demonstrated by secretion of proinflammatory cytokines; however, re-stimulation resulted in a diminished response. This observation may be explained by phenomena termed chronic inflammation adaptation response (Sundblad et al, 2009;May et al, 2012) in which repetitive dust exposure yields a less severe response in agriculture workers compared to naïve subjects.…”

Section: Discussionsupporting

confidence: 84%

Exposure to Swine Housing Dust Modulates Macrophage Morphology and Function

Pender

Minor

Hurley

et al. 2014

American Journal of Immunology

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Swine Confinement Facility (SCF) dust consists of a complex mixture of feed grain particles, bacterial components, organic particulates and gases. When these particles are inhaled they deposit along the respiratory tract and mediate respiratory symptoms and disease in swine farmers and facility workers. Macrophages ingest and eliminate microbes and debris under chronic conditions; however, the role of macrophages in agricultural-related respiratory disease has not been fully elucidated. The goal was to evaluate the hypothesis that chronic exposure to SCF dust causes inflammation by modulating pulmonary protein levels and macrophage function. Balb/c mice were exposed to 5, 12.5 and 25% SCF Dust Extract (DE) via nebulization 30 min/day five days a week, for eight weeks with weekends excluded. Bronchoalveolar Lavage Fluid (BALF) was collected and analyzed for protein concentration, leukocyte distribution and macrophage morphology. For comparison, THP-1 monocytic cells were exposed to 0.1-10% DE overnight and evaluated for phagocytosis and reactive oxygen species production. Repeated exposure to DE via nebulizer caused a significant increase in protein concentration and inflammatory cell number, namely macrophages, in a dose-dependent manner within the lung as compared to controls. Macrophages with pseudopods and vacuoles were the most abundant leukocytes within BALF of mice exposed to DE. Similarly, in vitro studies with 10% DE treated THP-1 cells revealed enhanced phagocytosis (p<0.05), pseudopodia and vacuolization following exposure to compared to control cells. In addition, there were time-and dose-dependent increases of intracellular ROS production by THP-1 cells exposed to 5 and 10% DE compared to control (p<0.01). These findings indicate repeated, long-term inhalation of swine confinement facility dust may mediate chronic airway and lung inflammation through modulation of protein concentration and macrophage function. The aerosolized dust-mouse inhalation model presented here may offer a good tool for studying particle mediated chronic inflammation of the tracheobronchial tree and lungs.

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“…We have previously found, in vitro, that single exposure to this dust induces significant secretion of proinflammatory mediators (TNF␣, IL-6, IL-8) in human epithelial cells and monocytes/macrophages, and that this response is, in part, regulated through PKC activity, particularly the PKC␣ and PKCε isoforms (31,32). In addition, repeat dust exposure results in an adaptation/ tolerance response in human monocytes (31), and repetitive dust exposure impairs the differentiation and function of macrophages derived from monocytes (30). However, the mechanisms underlying this apparent modulated inflammatory response to single vs. repetitive dust exposures in vivo are not clear.…”

mentioning

confidence: 99%

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

Poole¹,

Wyatt²,

Oldenburg³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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258

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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.

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Repeat organic dust exposure–induced monocyte inflammation is associated with protein kinase C activity

Abstract: Targeting PKC and specific mediators associated with repetitive organic dust exposure may result in novel therapeutic strategies.

Cited by 43 publications

References 29 publications

Repetitive organic dust exposure in vitro impairs macrophage differentiation and function

Repetitive organic dust exposure in vitro impairs macrophage differentiation and function

Exposure to Swine Housing Dust Modulates Macrophage Morphology and Function

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

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