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

Authors
Poole-JA; Wyatt-TA; Oldenburg-PJ; Elliott-MK; West-WW; Sisson-JH; Von Essen-SG; Romberger-DJ
Source
Am J Physiol, Lung Cell Mol Physiol 2009 Jun; 296(6):L1085-L1095
NIOSHTIC No.
20035639
Abstract
Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. 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 TNFalpha, 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 PKCalpha and -epsilon 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.
Keywords
Worker-health; Work-environment; Occupational-hazards; Safety-measures; Lung-burden; Lung-irritants; Bronchial-asthma; Dust-particles; Dusts; Agricultural-workers; Lung-cells; Cell-biology; Cell-function; Cell-migration; Respiratory-system-disorders; Pulmonary-system-disorders; Author Keywords: antigen presenting cell; phagocytosis; cytokines; aggregate; airway hyperresponsiveness
Contact
J. A. Poole, Pulmonary, Critical Care, Sleep, and Allergy Section, Univ. of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
CODEN
APLPE7
Publication Date
20090601
Document Type
Journal Article
Email Address
japoole@unmc.edu
Funding Type
Grant
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008539
Issue of Publication
6
ISSN
1040-0605
Priority Area
Agriculture, Forestry and Fishing
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
NE
Performing Organization
University of Nebraska
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