Scavenger Receptor BI Attenuates IL-17A–Dependent Neutrophilic Inflammation in Asthma

Asthma is a common respiratory disease currently affecting more than 300 million worldwide and is characterized by airway inflammation, hyperreactivity, and remodeling. It is a heterogeneous disease consisting of corticosteroid-sensitive T-helper cell type 2–driven eosinophilic and corticosteroid-resistant, T-helper cell type 17-driven neutrophilic phenotypes. One pathway recently described to regulate asthma pathogenesis is cholesterol trafficking. Scavenger receptors, in particular SR-BI (scavenger receptor class B type I), are known to direct cellular cholesterol uptake and efflux. We recently defined SR-BI functions in pulmonary host defense; however, the function of SR-BI in asthma pathogenesis is unknown. To elucidate the role of SR-BI in allergic asthma, SR-BI–sufficient (SR-BI(+/+)) and SR-BI–deficient (SR-BI(−/−)) mice were sensitized (Days 0 and 7) and then challenged (Days 14, 15, and 16) with a house dust mite (HDM) preparation administered through oropharyngeal aspiration. Airway inflammation and cytokine production were quantified on Day 17. When compared with SR-BI(+/+) mice, the HDM-challenged SR-BI(−/−) mice had increased neutrophils and pulmonary IL-17A production in BAL fluid. This augmented IL-17A production in SR-BI(−/−) mice originated from a non–T-cell source that included neutrophils and alveolar macrophages. Given that SR-BI regulates adrenal steroid hormone production, we tested whether the changes in SR-BI(−/−) mice were glucocorticoid dependent. Indeed, SR-BI(−/−) mice were adrenally insufficient during the HDM challenge, and corticosterone replacement decreased pulmonary neutrophilia and IL-17A production in SR-BI(−/−) mice. Taken together, these data indicate that SR-BI dampens pulmonary neutrophilic inflammation and IL-17A production in allergic asthma at least in part by maintaining adrenal function

Prairie Sandreed Response to Preceding-Year Defoliation and Precipitation Regime

Knowledge of how current-year grazing and drought stress affect subsequent-year herbage production is needed to enhance the management of semiarid Sandhills prairies. This study quantifies subsequent- year effects of defoliation and precipitation on prairie sandreed (Calamovilfa longijolia), a high-seral, warm-season tallgrass, and total graminoid herbage production in the Nebraska Sandhills. Mainplots (9.0 m2) received either ambient precipitation (noncovered) or precipitation was excluded during April-May, June-July, or August-September, resulting in 66% to 135% of the long-term average (434 mm) precipitation. All species in 1.0 m2 defoliated subplots were clipped in early July at the stubble height required for 30%, 60%, or 90% defoliation of C. longifolia. Measurements were made during July of the following year. Yield of C. longifolia declined about 5% for each 10 percentage points of defoliation compared to 3% yield declines for all graminoids (grasses and sedges) combined, regardless of precipitation regime. Additionally, excluding precipitation during June-July reduced tiller density by about 44% and yield and percent composition of C. longifolia by about 25% compared to ambient precipitation. Periodic full growing-season deferment may be necessary to maintain high-seral species dominance in these grassland communities, particularly in pastures where overgrazing and drought stress occur concurrently during June or July

Pulmonary Exposure to Magnéli Phase Titanium Suboxides Results in Significant Macrophage Abnormalities and Decreased Lung Function

Coal is one of the most abundant and economic sources for global energy production. However, the burning of coal is widely recognized as a significant contributor to atmospheric particulate matter linked to deleterious respiratory impacts. Recently, we have discovered that burning coal generates large quantities of otherwise rare Magnéli phase titanium suboxides from TiO2 minerals naturally present in coal. These nanoscale Magnéli phases are biologically active without photostimulation and toxic to airway epithelial cells in vitro and to zebrafish in vivo. Here, we sought to determine the clinical and physiological impact of pulmonary exposure to Magnéli phases using mice as mammalian model organisms. Mice were exposed to the most frequently found Magnéli phases, Ti6O11, at 100 parts per million (ppm) via intratracheal administration. Local and systemic titanium concentrations, lung pathology, and changes in airway mechanics were assessed. Additional mechanistic studies were conducted with primary bone marrow derived macrophages. Our results indicate that macrophages are the cell type most impacted by exposure to these nanoscale particles. Following phagocytosis, macrophages fail to properly eliminate Magnéli phases, resulting in increased oxidative stress, mitochondrial dysfunction, and ultimately apoptosis. In the lungs, these nanoparticles become concentrated in macrophages, resulting in a feedback loop of reactive oxygen species production, cell death, and the initiation of gene expression profiles consistent with lung injury within 6 weeks of exposure. Chronic exposure and accumulation of Magnéli phases ultimately results in significantly reduced lung function impacting airway resistance, compliance, and elastance. Together, these studies demonstrate that Magnéli phases are toxic in the mammalian airway and are likely a significant nanoscale environmental pollutant, especially in geographic regions where coal combustion is a major contributor to atmospheric particulate matter