Sheena D. Brown

Impaired Terminal Differentiation of Pulmonary Macrophages in a Guinea Pig Model of Chronic Ethanol Ingestion

BACKGROUND Alcoholic patients have an increased risk of respiratory infections, which is partially due to an impaired immune response of alveolar macrophages. The mechanisms by which alcohol impairs alveolar macrophage function are poorly understood. In this study, we demonstrated in a guinea pig model that chronic ethanol ingestion significantly impaired alveolar macrophage differentiation and function. METHODS Isolated alveolar macrophages were separated into 4 different subpopulations with varying densities and levels of maturation. RESULTS Compared to control values, chronic ethanol ingestion decreased the percentage of alveolar macrophages in the mature fractions by approximately 60%. Alveolar macrophage function in each subpopulation was determined by measuring phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus aureus. Alveolar macrophages from ethanol-fed animals had approximately 80% decrease in the phagocytic index. Western blot and immunohistochemical analysis of the differential markers granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor alpha (GM-CSFR-alpha), PU.1, CD11c, and CD11b verified that alcoholic macrophages displayed impaired terminal differentiation. While oral supplementation with the glutathione precursor S-adenosyl-methionine (SAM) did not alter the maturational status of control animals, SAM supplementation shifted the distribution of macrophages to more mature fractions, normalized the phagocytic index; as well as normalized expression of CD11c, CD11b, PU.1, and GM-CSFR-alpha. Chronic ethanol ingestion also impaired the differentiation status of interstitial macrophages which was normalized by SAM supplementation. CONCLUSION This improvement in the maturational status suggested that ethanol-induced oxidant stress is a central feature in impaired terminal differentiation of macrophages in the interstitial and alveolar space. Therefore, strategies targeting pulmonary oxidant stress may restore macrophage differentiation and function even after chronic ethanol ingestion.

Vitamin D and asthma

Asthma, one of the most prevalent diseases affecting people worldwide, is a chronic respiratory disease characterized by heightened airway inflammation, airway hyperresponsiveness and airflow obstruction in response to specific triggers. While the specific mechanisms responsible for asthma are not well understood, changing environmental factors associated with urban lifestyles may underlie the increased prevalence of the disorder. Vitamin D is of particular interest in asthma since vitamin D concentrations decrease with increased time spent indoors, decreased exposure to sunlight, less exercise, obesity, and inadequate calcium intake. Additionally, a growing body of literature suggests that there is a relationship between vitamin D status and respiratory symptoms, presumably through immunomodulatory effects of vitamin D. This review discusses vitamin D as it relates to asthma across the age spectrum, with a focus on human studies.

Characterization of a high TNF-α phenotype in children with moderate-to-severe asthma

Systemic TNF-α expression is increased in a subset of children with moderate-to-severe asthma despite aggressive corticosteroid treatment and is associated with poor asthma control. Phenotypic-directed TNF-α inhibition may be of benefit in some asthmatic children.

Letter to the editorCharacterization of a high TNF-α phenotype in children with moderate-to-severe asthma

Systemic TNF-α expression is increased in a subset of children with moderate-to-severe asthma despite aggressive corticosteroid treatment and is associated with poor asthma control. Phenotypic-directed TNF-α inhibition may be of benefit in some asthmatic children.