Chronic Alcohol Ingestion Impairs Rat Alveolar Macrophage Phagocytosis via Disruption of RAGE Signaling.

Background: Alcohol significantly impairs antioxidant defenses and innate immune function in the lung and increases matrix metalloproteinase 9 (MMP-9) activity. The receptor for advanced glycation end products (RAGE) is a well-characterized marker of lung injury that is cleaved by MMP-9 into soluble RAGE and has not yet been examined in the alcoholic lung. We hypothesized that chronic alcohol ingestion would impair RAGE signaling via MMP-9 in the alveolar macrophage and thereby impair innate immune function.

Pulmonary Innate Immune Dysfunction in Human Immunodeficiency Virus.

The advent of antiretroviral therapy has transformed infection by the type 1 human immunodeficiency virus (HIV) from a rapidly fatal disease to a chronic illness with excellent long-term survival rates. Although HIV primarily targets the adaptive arm of host immunity, it simultaneously impacts the innate immune system, and has profound implications for lung health, even when viral suppression is achieved with antiretroviral therapy. The lung has evolved a unique array of innate immune defenses, and the pathophysiological interactions between HIV and the pulmonary innate immune system deserve particular attention.

Activation of Alveolar Macrophages with Interferon-γ Promotes Antioxidant Defenses via the Nrf2-ARE Pathway.

Macrophage phenotype and function is dependent on the underlying microenvironment. Many diseases are accompanied by abnormal shifts in macrophage polarization state that limit the ability of the cells to become innate immune effectors. Previous work in the field suggests that chronic alcohol ingestion, which is associated with a shift away from innate immune effector macrophages, is also associated with a deficient response to oxidative stress.

Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth.

Lung cancer is the leading cause of cancer death worldwide. Recent data suggest that tumor-associated inflammatory cells may modify lung tumor growth and invasiveness. To determine the role of neutrophil elastase (encoded by Elane) on tumor progression, we used the loxP-Stop-loxP K-ras(G12D) (LSL-K-ras) model of mouse lung adenocarcinoma to generate LSL-K-ras-Elane(-/-) mice.

Epithelial cell apoptosis causes acute lung injury masquerading as emphysema.

Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement.