A Role for B Cells in Organic Dust Induced Lung Inflammation
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2017/12/22
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Description:BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity. METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected. RESULTS: ODE-induced neutrophil influx in lavage fluid was not reduced in BCR KO animals, but there was reduction in TNF-alpha, IL-6, CXCL1, and CXCL2 release. ODE-induced lymphoid aggregates failed to develop in BCR KO mice. There was a decrease in ODE-induced lung tissue CD11c+CD11b+ exudative macrophages and compensatory increase in CD8+ T cells in lavage fluid of BCR KO animals. Compared to saline, there was an expansion of conventional B2-, innate B1 (CD19+CD11b+CD5+/-)-, and memory (CD19+CD273+/-CD73+/-) B cells following ODE exposure in WT mice. Autoreactive responses including serum IgG anti-citrullinated protein antibody (ACPA) and anti-malondialdehyde-acetaldehyde (MAA) autoantibodies were increased in ODE treated WT mice as compared to saline control. B cells and serum immunoglobulins were not detected in BCR KO animals. CONCLUSIONS: Lung tissue staining for citrullinated and MAA modified proteins were increased in ODE-treated WT animals, but not BCR KO mice. These studies show that agriculture organic dust induced lung inflammation is dependent upon B cells, and dust exposure induces an autoreactive response. [Description provided by NIOSH]
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ISSN:1465-9921
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Volume:18
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NIOSHTIC Number:nn:20050744
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Citation:Respir Res 2017 Dec; 18:214
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Contact Point Address: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
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Email:japoole@unmc.edu
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Federal Fiscal Year:2018
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Performing Organization:University of Nebraska Medical Center - Omaha
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Peer Reviewed:True
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Start Date:20110901
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Source Full Name:Respiratory Research
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End Date:20270831
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Main Document Checksum:urn:sha-512:67da2296bf08aff83fb2ba941380b38061410534f5e8625a602520b44b21f30fb9f7c677dda7202fd4794536c4ca55e289f1e8bafe28d7357fa78467d2b133df
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