Post-Injury and Resolution Response to Repetitive Inhalation Exposure to Agricultural Organic Dust in Mice
Kristi J. Warren,
Todd A. Wyatt,
Debra J. Romberger,
Isaak Ailts,
William W. West,
Amy J. Nelson,
Tara M. Nordgren,
Elizabeth Staab,
Art J. Heires,
Jill A. Poole
Affiliations
Kristi J. Warren
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
Todd A. Wyatt
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
Debra J. Romberger
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
Isaak Ailts
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
William W. West
Department of Pathology and Microbiology, UNMC, 983135 Nebraska Medical Center, Omaha, NE 681983135, USA
Amy J. Nelson
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
Tara M. Nordgren
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
Elizabeth Staab
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
Art J. Heires
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
Jill A. Poole
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
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.
