Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice.
Poole JA; Wyatt TA; Oldenburg PJ; Elliott MK; West WW; Sisson JH; Von Essen SG; Romberger DJ
Am J Physiol, Lung Cell Mol Physiol 2009 Jun; 296(6):L1085-L1095
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.
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
J. A. Poole, Pulmonary, Critical Care, Sleep, and Allergy Section, Univ. of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
Agriculture, Forestry and Fishing
American Journal of Physiology: Lung Cellular and Molecular Physiology
University of Nebraska Medical Center, Omaha, Nebraska