Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium

Breidenbach, Joshua D.; French, Benjamin W.; Gordon, Tamiya T.; Kleinhenz, Andrew L.; Khalaf, Fatimah K.; Willey, James C.; Hammersley, Jeffrey R.; Mark Wooten, R.; Crawford, Erin L.; Modyanov, Nikolai N.; Malhotra, Deepak; Teeguarden, Justin G.; Haller, Steven T.; Kennedy, David J.

doi:10.1016/j.envint.2022.107531

Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium

Journal Article · Sat Sep 17 00:00:00 EDT 2022 · Environment International

DOI:https://doi.org/10.1016/j.envint.2022.107531· OSTI ID:1893823

Breidenbach, Joshua D. ^[1]; French, Benjamin W. ^[1]; Gordon, Tamiya T. ^[1]; Kleinhenz, Andrew L. ^[1]; Khalaf, Fatimah K. ^[2]; Willey, James C. ^[1]; Hammersley, Jeffrey R. ^[1]; Mark Wooten, R. ^[1]; Crawford, Erin L. ^[1]; Modyanov, Nikolai N. ^[1]; Malhotra, Deepak ^[1]; ^[3]; Haller, Steven T. ^[1]; Kennedy, David J. ^[1]

University of Toledo, OH (United States)
University of Toledo, OH (United States); University of Alkafeel, Najaf (Iraq)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States); Oregon State University, Corvallis, OR (United States)

Harmful algal blooms plague bodies of freshwater globally. These blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide Microcystin-LR (MC-LR) which is a well-known hepatotoxin. Recently, MC-LR has been detected in aerosols generated from lake water. However, the risk for human health effects due to MC-LR inhalation exposure have not been extensively investigated. In this study, we exposed a fully differentiated 3D human airway epithelium derived from 14 healthy donors to MC-LR-containing aerosol for 3 minutes per day for 3 days. Concentrations of MC-LR ranged from 100 pM to 1 µM. Although there were little to no detrimental alterations in measures of the airway epithelial function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct shift in the transcriptional activity was found. Genes related to inflammation were found to be upregulated such as C-C motif chemokine 5 (CCL5; log2FC = 0.56 , p = 0.02) and C-C chemokine receptor type 7 (CCR7; log2FC = 0.83, p = 0.03). Functionally, conditioned media from MC-LR exposed airway epithelium was also found to have significant chemo-attractive properties for primary human neutrophils. Additionally, increases were found in the concentration of secreted chemokine proteins in the conditioned media such as CCL1 (log2FC = 5.07 , p = 0.0001) and CCL5 (log2FC = 1.02, p = 0.046). These results suggest that MC-LR exposure to the human airway epithelium is capable of inducing an inflammatory response that may potentiate acute or chronic disease.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: David and Helen Boone Foundation; German Federal Ministry of Education and Research; German Research Council (DFG); National Institutes of Health (NIH); Ohio Department of Higher Education; Philanthropy Genetic Analysis Instrumentation Center; USDOE; University of Toledo

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1893823

Report Number(s):: PNNL-SA-174435

Journal Information:: Environment International, Journal Name: Environment International Vol. 169; ISSN 0160-4120

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
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inflammation
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Microcystin-LR aerosol induces inflammatory responses in healthy human primary airway epithelium

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