Emerging Insights into the Impact of Air Pollution on Immune-Mediated Asthma Pathogenesis.

PURPOSE OF REVIEW: Increases in ambient levels of air pollutants have been linked to lung inflammation and remodeling, processes that lead to the development and exacerbation of allergic asthma. Conventional research has focused on the role of CD4+ T helper 2 (TH2) cells in the pathogenesis of air pollution-induced asthma. However, much work in the past decade has uncovered an array of air pollution-induced non-TH2 immune mechanisms that contribute to allergic airway inflammation and disease. RECENT FINDINGS: In this article, we review current research demonstrating the connection between common air pollutants and their downstream effects on non-TH2 immune responses emerging as key players in asthma, including PRRs, ILCs, and non-TH2 T cell subsets. We also discuss the proposed mechanisms by which air pollution increases immune-mediated asthma risk, including pre-existing genetic risk, epigenetic alterations in immune cells, and perturbation of the composition and function of the lung and gut microbiomes. Together, these studies reveal the multifaceted impacts of various air pollutants on innate and adaptive immune functions via genetic, epigenetic, and microbiome-based mechanisms that facilitate the induction and worsening of asthma.

Novel Mechanisms of Ozone-Induced Pulmonary Inflammation and Resolution, and the Potential Protective Role of Scavenger Receptor BI.

INTRODUCTION: Increases in ambient levels of ozone (O3), a criteria air pollutant, have been associated with increased susceptibility and exacerbations of chronic pulmonary diseases through lung injury and inflammation. O3 induces pulmonary inflammation, in part by generating damage-associated molecular patterns (DAMPs), which are recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and scavenger receptors (SRs). This inflammatory response is mediated in part by alveolar macrophages (AMs), which highly express PRRs, including scavenger receptor BI (SR-BI). Once pulmonary inflammation has been induced, an active process of resolution occurs in order to prevent secondary necrosis and to restore tissue homeostasis. The processes known to promote the resolution of inflammation include the clearance by macrophages of apoptotic cells, known as efferocytosis, and the production of specialized pro-resolving mediators (SPMs). Impaired efferocytosis and production of SPMs have been associated with the pathogenesis of chronic lung diseases; however, these impairments have yet to be linked with exposure to air pollutants. SPECIFIC AIMS: The primary goals of this study were: Aim 1 - to define the role of SR-BI in O3-derived pulmonary inflammation and resolution of injury; and Aim 2 - to determine if O3 exposure alters pulmonary production of SPMs and processes known to promote the resolution of pulmonary inflammation and injury. METHODS: To address Aim 1, female wild-type (WT) and SR-BI-deficient, or knock-out (SR-BI KO), mice were exposed to either O3 or filtered air. In one set of experiments mice were instilled with an oxidized phospholipid (oxPL). Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for the analyses of inflammatory and injury markers and oxPL. To estimate efferocytosis, mice were administered apoptotic cells (derived from the Jurkat T cell line) after O3 or filtered air exposure.To address Aim 2, male WT mice were exposed to either O3 or filtered air, and levels of SPMs were assessed in the lung, as well as markers of inflammation and injury in BALF. In some experiments SPMs were administered before exposure to O3or filtered air, to determine whether SPMs could mitigate inflammatory or resolution responses. Efferocytosis was measured as in Aim 1. RESULTS: For Aim 1, SR-BI protein levels increased in the lung tissue of mice exposed to O3, compared with mice exposed to filtered air. Compared with WT controls, SR-BI KO mice had a significant increase in the number of neutrophils in their airspace 24 hours post O3 exposure. The oxPL levels increased in the airspace of both WT and SR-BI KO mice after O3 exposure, compared with filtered air controls. Four hours after instillation of an oxPL, SR-BI KO mice had an increase in BALF neutrophils and total protein, and a nonsignificant increase in macrophages compared with WT controls. O3 exposure decreased efferocytosis in both WT and SR-BI KO female mice.For Aim 2, mice given SPM supplementation before O3 exposure showed significantly increased AM efferocytosis when compared with the O3exposure control mice and also showed some mitigation of the effects of O3 on inflammation and injury. Several SPMs and their precursors were measured in lung tissue using reverse-phase high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). At 24 hours after O3 exposure 14R-hydroxydocosahexaenoic acid (HDHA) and 10,17-dihydroxydocosahexaenoic acid (diHDoHE) were significantly decreased in lung tissue, but at 6 hours after exposure, levels of these SPMs increased. CONCLUSIONS: Our findings identify novel mechanisms by which O3 may induce pulmonary inflammation and also increase susceptibility to and exacerbations of chronic lung diseases.

Electrostatic dust collectors compared to inhalable samplers for measuring endotoxin concentrations in farm homes.

Paired electrostatic dust collectors (EDCs) and daily, inhalable button samplers (BS) were used concurrently to sample endotoxin in 10 farm homes during 7-day periods in summer and winter. Winter sampling included an optical particle counter (OPC) to measure PM2.5 and PM2.5-10 . Electrostatic dust collectors and BS filters were analyzed for endotoxin using the kinetic chromogenic Limulus amebocyte lysate assay. Optical particle counter particulate matter (PM) data were divided into two PM categories. In summer, geometric mean (geometric standard deviation) endotoxin concentrations were 0.82 EU/m(3) (2.7) measured with the BS and 737 EU/m(2) (1.9) measured with the EDC. Winter values were 0.52 EU/m(3) (3.1) for BS and 538 EU/m(2) (3.0) for EDCs. Seven-day endotoxin values of EDCs were highly correlated with the 7-day BS sampling averages (r = 0.70; P < 0.001). Analysis of variance indicated a 2.4-fold increase in EDC endotoxin concentrations for each unit increase of the ratio of PM2.5 to PM2.5-10 . There was also a significant correlation between BS and EDCs endotoxin concentrations for winter (r = 0.67; P < 0.05) and summer (r = 0.75; P < 0.05). Thus, EDCs sample comparable endotoxin concentrations to BS, making EDCs a feasible, easy to use alternative to BS for endotoxin sampling.