Aerosolized aqueous dust extracts collected near a drying lake trigger acute neutrophilic pulmonary inflammation reminiscent of microbial innate immune ligands

Biddle, Trevor; Yisrael, Keziyah; Drover, Ryan; Li, Qi; Maltz, Mia R.; Topacio, Talyssa M.; Yu, Jasmine; Castillo, Diana Del; Gonzales, Daniel; Freund, Hannah L.; Swenson, Mark P.; Shapiro, Malia L.; Botthoff, Jon; Aronson, E. L.; Cocker, David R.; Lo, David

doi:10.1016/j.scitotenv.2022.159882

Cited by 2 publications

(1 citation statement)

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“…Aerosol exposures were conducted using dual animal chambers as developed and characterized in Peng et al (2019) and used in Biddle et al (2021Biddle et al ( , 2023 [10,11]. The conditions in the chambers were monitored for the duration of the exposures, including relative humidity, temperature, and atmospheric pressure.…”

Section: Aerosol Exposure Chambermentioning

confidence: 99%

Route of administration significantly affects particle deposition and cellular recruitment

Yisrael,

Drover,

Shapiro

et al. 2023

PLoS ONE

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Lung exposures to dusts, pollutants, and other aerosol particulates are known to be associated with pulmonary diseases such as asthma and Chronic Obstructive Pulmonary Disease. These health impacts are attributed to the ability of aerosol components to induce pulmonary inflammation, which promotes tissue remodeling, including fibrosis, tissue degradation, and smooth muscle proliferation. Consequently, the distribution of these effects can have a significant impact on the physiologic function of the lung. In order to study the impact of distribution of inhaled particulates on lung pathogenesis, we compared the effect of different methods of particle delivery. By comparing intranasal versus aerosol delivery of fluorescent microspheres, we observed strikingly distinct patterns of particle deposition; intranasal delivery provided focused deposition concentrated on larger airways, while aerosol delivery showed unform deposition throughout the lung parenchyma. Recognizing that the impacts of inflammatory cells are contingent upon their recruitment and behavior, we postulate that these variations in distribution patterns can result in significant alterations in biological responses. To elucidate the relevance of these findings in terms of biological representation, we subsequently conducted an investigation into the responses elicited by the administration of endotoxin (bacterial Lipopolysaccharide, or LPS) in a transgenic neutrophil reporter mouse model. As with the microsphere results, patterns of recruited neutrophil inflammatory responses matched the delivery method; that is, despite the active migratory behavior of neutrophils, inflammatory histopathology patterns were either focused on large airways (intranasal administration) or diffusely throughout the parenchyma (aerosol). These results demonstrate the importance of modes of aerosol delivery as different patterns of inflammation and tissue remodeling will have distinct impacts on lung physiology.

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Section: Aerosol Exposure Chambermentioning

confidence: 99%