Safety 2017, 3(1), 10; https://doi.org/10.3390/safety3010010
Post-Injury and Resolution Response to Repetitive Inhalation Exposure to Agricultural Organic Dust in Mice
Kristi J. Warren 1, Todd A. Wyatt 1,2,3, Debra J. Romberger 1,2, Isaak Ailts 1, William W. West 4, Amy J. Nelson 1, Tara M. Nordgren 1
, Elizabeth Staab 1, Art J. Heires 1,2 and Jill A. Poole 1,*
, Elizabeth Staab 1, Art J. Heires 1,2 and Jill A. Poole 1,*
1
Pulmonary, Critical Care, Sleep & Allergy Division; Department of Internal Medicine, University of Nebraska Medical Center (UNMC), 985990 Nebraska Medical Center, Omaha, NE 68198-5990, USA
2
Department of Environmental, Agricultural, and Occupational Health, University of Nebraska Medical Center, 985990 Nebraska Medical Center, Omaha, NE 68198-5990, USA
3
Veterans Affairs Nebraska-Western Iowa Health Care System, 4101 Woolworth St., Omaha, NE 68105, USA
4
Department of Pathology and Microbiology, UNMC, 983135 Nebraska Medical Center, Omaha, NE 681983135, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dennis Murphy
Received: 30 June 2016 / Accepted: 10 February 2017 / Published: 21 February 2017
(This article belongs to the Special Issue Agricultural Safety and Health)
Abstract
Inhalation of organic dusts in agricultural environments causes airway inflammatory diseases. Despite advances in understanding the airway response to dust-induced inflammation, less is known about the transition from lung injury to repair and recovery. The objective of this study was to define the post-inflammation homeostasis events following organic dust-induced lung injury. Using an established protocol, mice were intranasally treated with swine confinement facility organic dust extract (ODE) daily for 3 weeks (repetitive exposure) or treated daily with ODE for 3 weeks followed by no treatment for 1-4 weeks (recovery period) whereupon lavage fluid, lung tissue, and sera were processed. During recovery period, a significant decrease was observed in ODE-induced neutrophil levels after 1 week, lymphocytes at 2 weeks, and macrophages at 4 weeks in the lavage fluid. ODE-induced lung cellular aggregates and bronchiolar compartment inflammation were diminished, but persisted for 4 weeks post-injury. Alveolar inflammation resolved at 3 weeks. ODE-induced lung neutrophils were cleared by 3 weeks, B-cells by 2 weeks, and CD3+CD4+ and CD3+CD8+ T cells by 4 week recovery period. Amphiregulin levels increased post-ODE exposure to the 4 week recovery period. Ex vivo amphiregulin production was demonstrated in lung type 2 innate lymphoid cells and macrophages isolated from the 4 week recovery (post-ODE exposure) animals. Collectively, these results identify important processes during recovery period following agricultural dust-induced inflammation, and present possible strategies for improving lung repair and resolution. View Full-TextKeywords:
lung; repair; inflammation; resolution; lymphocyte; agriculture; farm; neutrophil; immunity; swine barn; amphiregulin; innate lymphoid cells; ILC2
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Warren, K.J.; Wyatt, T.A.; Romberger, D.J.; Ailts, I.; West, W.W.; Nelson, A.J.; Nordgren, T.M.; Staab, E.; Heires, A.J.; Poole, J.A. Post-Injury and Resolution Response to Repetitive Inhalation Exposure to Agricultural Organic Dust in Mice. Safety 2017, 3, 10.
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