Low- and high-LET radiation drives clonal expansion of lung progenitor cells in vivo.

Abundant populations of epithelial progenitor cells maintain the epithelium along the proximal-to-distal axis of the airway. Exposure of lung tissue to ionizing radiation leads to tissue remodeling and potential cancer initiation or progression. However, little is known about the effects of ionizing radiation on airway epithelial progenitor cells.

Impaired CD8(+) T cell immunity after allogeneic bone marrow transplantation leads to persistent and severe respiratory viral infection.

Rationale: Bone marrow transplant (BMT) recipients experience frequent and severe respiratory viral infections (RVIs). However, the immunological mechanisms predisposing to RVIs are uncertain. Therefore, we hypothesized that antiviral T cell immunity is impaired as a consequence of allogeneic BMT, independent of pharmacologic immunosuppression, and is responsible for increased susceptibility to RVI.

Diesel exhaust particles induce aberrant alveolar epithelial directed cell movement by disruption of polarity mechanisms.

Disruption of the respiratory epithelium contributes to the progression of a variety of respiratory diseases that are aggravated by exposure to air pollutants, specifically traffic-based pollutants such as diesel exhaust particles (DEP). Recognizing that lung repair following injury requires efficient and directed alveolar epithelial cell migration, this study's goal was to understand the mechanisms underlying alveolar epithelial cells response to DEP, particularly when exposure is accompanied with comorbid lung injury. Separate mechanistic steps of directed migration were investigated in confluent murine LA-4 cells exposed to noncytotoxic concentrations (0-100 μg/cm(2)) of either automobile-emitted diesel exhaust particles (DEP(A)) or carbon black (CB) particles.

Nitric oxide and superoxide mediate diesel particle effects in cytokine-treated mice and murine lung epithelial cells--implications for susceptibility to traffic-related air pollution.

Background: Epidemiologic studies associate childhood exposure to traffic-related air pollution with increased respiratory infections and asthmatic and allergic symptoms. The strongest associations between traffic exposure and negative health impacts are observed in individuals with respiratory inflammation. We hypothesized that interactions between nitric oxide (NO), increased during lung inflammatory responses, and reactive oxygen species (ROS), increased as a consequence of traffic exposure ─ played a key role in the increased susceptibility of these at-risk populations to traffic emissions.

Amphiregulin-dependent mucous cell metaplasia in a model of nonallergic lung injury.

Proliferation and differentiation of the pulmonary epithelium after injury is a critical process in the defense against the external environment. Defects in this response can result in airway remodeling, such as mucus cell metaplasia (MCM), commonly seen in patients with chronic lung disease. We have previously shown that amphiregulin (AREG), a ligand to the epidermal growth factor receptor (EGFR), is induced during the repair/differentiation process elicited by naphthalene-induced lung injury.

Susceptibility of inflamed alveolar and airway epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content.

Exposure to traffic-related ambient air pollution, such as diesel exhaust particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting inflammatory respiratory diseases. Using an analogous novel in vitro system to model both the healthy and inflamed lung, the susceptibility of epithelial cells exposed to DEP of varying organic carbon content was studied. Murine LA-4 alveolar type II-like epithelial cells, as well as primary murine tracheal epithelial cells (MTE), were treated with exogenous cytokines (tumor necrosis factor [TNF] alpha + interleukin [IL]-1 beta + interferon [IFN] gamma) to model a mild inflammatory state.

DNA damage induced by hyperoxia: quantitation and correlation with lung injury.

Inspired oxygen, an essential therapy for cardiorespiratory disorders, has the potential to generate reactive oxygen species that damage cellular DNA. Although DNA damage is implicated in diverse pulmonary disorders, including neoplasia and acute lung injury, the type and magnitude of DNA lesion caused by oxygen in vivo is unclear. We used single-cell gel electrophoresis (SCGE) to quantitate two distinct forms of DNA damage, base adduction and disruption of the phosphodiester backbone, in the lungs of mice.