Profiling endogenous airway proteases and antiproteases and modeling proteolytic activation of Influenza HA using in vitro and ex vivo human airway surface liquid samples.

Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported.

Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.

Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality.

Simulated burn pit smoke condensates cause sustained impact on human airway epithelial cells.

Inhalation of smoke from burn pits during military deployment is associated with several adverse pulmonary outcomes. We exposed human airway epithelial cells to smoke condensates from burn pit waste materials. Single and repeated exposure of condensates triggered unique and common responses in terms of gene expression, that sustained through the recovery phase.

Comparison of permeable cell culture inserts for use in culture of a human in vitro air-liquid interface model system.

In this study, we compared 12 mm cell culture inserts with permeable polyester membranes (0.4 μm pores) from two different manufacturers: CELLTREAT® and Corning®. Physical dimensions and masses of the inserts were found to be very similar between the two brands, with CELLTREAT® inserts having a slightly smaller diameter and growth area (11.

Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.

Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users ( = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury.

Woodsmoke particle exposure prior to SARS-CoV-2 infection alters antiviral response gene expression in human nasal epithelial cells in a sex-dependent manner.

Inhalational exposure to particulate matter (PM) derived from natural or anthropogenic sources alters gene expression in the airways and increases susceptibility to respiratory viral infection. Woodsmoke-derived ambient PM from wildfire events during 2020 was associated with higher COVID-19 case rates in the western United States. We hypothesized that exposure to suspensions of woodsmoke particles (WSPs) or diesel exhaust particles (DEPs) prior to SARS-CoV-2 infection would alter host immune gene expression at the transcript level.

Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner.

We have previously shown that exposure to particulate air pollution, both from natural and anthropogenic sources, alters gene expression in the airways and increases susceptibility to respiratory viral infection. Additionally, we have shown that woodsmoke particulates (WSP) affect responses to influenza in a sex-dependent manner. In the present study, we used human nasal epithelial cells (hNECs) from both sexes to investigate how particulate exposure could modulate gene expression in the context of SARS-CoV-2 infection.

Impact of inhaled pollutants on response to viral infection in controlled exposures.

Air pollutants are a major source of increased risk of disease, hospitalization, morbidity, and mortality worldwide. The respiratory tract is a primary target of potential concurrent exposure to both inhaled pollutants and pathogens, including viruses. Although there are various associative studies linking adverse outcomes to co- or subsequent exposures to inhaled pollutants and viruses, knowledge about causal linkages and mechanisms by which pollutant exposure may alter human respiratory responses to viral infection is more limited.

Prediction of Membrane Permeation of Drug Molecules by Combining an Implicit Membrane Model with Machine Learning.

Lipid membrane permeation of drug molecules was investigated with Heterogeneous Dielectric Generalized Born (HDGB)-based models using solubility-diffusion theory and machine learning. Free energy profiles were obtained for neutral molecules by the standard HDGB and Dynamic HDGB (DHDGB) to account for the membrane deformation upon insertion of drugs. We also obtained hybrid free energy profiles where the neutralization of charged molecules was taken into account upon membrane insertion.