nitrogen-dioxide and Respiratory-Syncytial-Virus-Infections

This study examined the effects of nitrogen dioxide (NO(2)) exposure on airway inflammation, blood cells, and antiviral respiratory defense. Twenty-one healthy volunteers were exposed on separate occasions to air and 0.6 and 1.5 ppm NO(2) for 3 h with intermittent moderate exercise. Phlebotomy and bronchoscopy were performed 3.5 h after each exposure, and recovered cells were challenged with respiratory viruses in vitro. Blood studies revealed a 4.1% NO(2) dose-related decrease in hematocrit (P = 0.003). Circulating total lymphocytes (P = 0.024) and T lymphocytes (P = 0.049) decreased with NO(2) exposure. Exposure to NO(2) increased the blood lymphocyte CD4(+)-to-CD8(+) ratio from 1.74 +/- 0.11 to 1.85 +/- 0.12 in males but decreased it from 1.88 +/- 0.19 to 1.78 +/- 0.19 in females (P < 0.001 for gender difference). Polymorphonuclear leukocytes in bronchial lavage increased with NO(2) exposure (P = 0.003). Bronchial epithelial cells obtained after exposure to 1.5 ppm NO(2) released 40% more lactate dehydrogenase after challenge with respiratory syncytial virus than with air exposure (P = 0.024). In healthy subjects, exposures to NO(2) at levels found indoors cause mild airway inflammation, effects on blood cells, and increased susceptibility of airway epithelial cells to injury from respiratory viruses.

Topics: Adult; Air; Blood Cells; Bronchi; Bronchoalveolar Lavage Fluid; CD4-CD8 Ratio; Cell Survival; Disease Susceptibility; Dose-Response Relationship, Drug; Double-Blind Method; Epithelial Cells; Female; Humans; Influenza, Human; L-Lactate Dehydrogenase; Lymphocytes; Male; Neutrophils; Nitrogen Dioxide; Phenotype; Respiratory Syncytial Virus Infections

Populations in Asia are not only at risk of harm to their health through environmental degradation as a result of worsening pollution problems but also constantly threatened by recurring and emerging influenza epidemics and. pandemics. Situated in the area with the world's fastest growing economy and close to hypothetical epicenters of influenza transmission, Hong Kong offers a special opportunity for testing environmental management and public health surveillance in the region. In the Public Health and Air Pollution in Asia (PAPA*) project, the Hong Kong research team assessed the health effects of air pollution and influenza as well as the interaction between them. The team also assessed disparities in the health effects of air pollution between relatively deprived and more affluent areas in Hong Kong. The aim was to provide answers to outstanding research questions relating to the short-term effects of air pollution on mortality and hospital admissions; the health effects of influenza with a view to validating different measures of influenza activity according to virologic data; the confounding effects of influenza on estimates of the health effects of air pollution; the modifying effects of influenza on the health effects of air pollution; and the modifying effects of neighborhood social deprivation on the health effects of air pollution.. Data on mortality and hospital admissions for all natural causes, as well as the subcategories of cardiovascular diseases (CVD) and respiratory diseases (RD), were derived from the Hong Kong Census and Statistics Department and the Hospital Authority. Daily concentrations of nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter with an aerodynamic diameter < or = 10 pm (PM10); and ozone (O3) were derived from eight monitoring stations with hourly data that were at least 75% complete during the study period. Three measures of influenza and respiratory syncytial virus (RSV) activity were derived from positive isolates of specimens in the virology laboratory of Queen Mary Hospital (QMH), the main clinical teaching center at The University of Hong Kong and part of the Hong Kong Hospital Authority network of teaching hospitals: influenza intensity (defined as the weekly proportion of positive isolates of influenza in the total number of specimens received for diagnostic tests); the presence of influenza epidemic (defined as a period when the weekly frequency of these positive isolates is > or = 4% of the annual total number of positive isolates [i.e., twice the expected mean value] in two or more consecutive weeks); and influenza predominance (defined as a period of influenza epidemic when the weekly frequency of RSV was less than 2% for two or more consecutive weeks). The weekly proportion of positive isolates of RSV in total specimens was determined in the same way as for influenza intensity. A social deprivation index (SDI) was defined by taking the average of the proportions of households or persons with the following six characteristics in each geographic area using the census statistics: unemployment; household income < U.S. $250 per month; no schooling at all; never-married status; one-person household; and subtenancy. A Poisson regression with quasi-likelihood to account for overdispersion was used to develop core models for daily health outcomes, with a natural spline smoothing function to filter out seasonal patterns and long-term trends in this time-series study of daily mortality and hospital admissions, and with adjustment for days of the week, temperature, and relative humidity (RH). Air pollutant concentration values were entered into the core model to assess the health effects of specific pollutants. The possible confounding effects of influenza were assessed by observing changes in magnitude of the effect estimate when each influenz

Topics: Adolescent; Adult; Age Factors; Aged; Air Pollutants; Air Pollution; Child; Child, Preschool; Female; Hong Kong; Humans; Infant; Infant, Newborn; Influenza, Human; Male; Middle Aged; Nitrogen Dioxide; Ozone; Particulate Matter; Patient Admission; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Seasons; Sex Factors; Sulfur Dioxide; Time Factors; Young Adult

3-nitrotyrosine (NO2Tyr), an L-tyrosine derivative during nitrative stress, can substitute the COOH-terminal tyrosine of alpha-tubulin, posttranslationally altering microtubular functions. Because infection of the cells by respiratory syncytial virus (RSV) may require intact microtubules, we tested the hypothesis that NO2Tyr would inhibit RSV infection and intracellular signaling via nitrotyrosination of alpha-tubulin. A human bronchial epithelial cell line (BEAS-2B) was incubated with RSV with or without NO2Tyr. The release of chemokines and viral particles and activation of interferon regulatory factor-3 (IRF-3) were measured. Incubation with NO2Tyr increased nitrotyrosinated alpha-tubulin, and NO2Tyr colocalized with microtubules. RSV-infected cells released viral particles, RANTES, and IL-8 in a time- and dose-dependent manner, and intracellular RSV proteins coprecipitated with alpha-tubulin. NO2Tyr attenuated the RSV-induced release of RANTES, IL-8, and viral particles by 50-90% and decreased alpha-tubulin-associated RSV proteins. 3-chlorotyrosine, another L-tyrosine derivative, had no effects. NO2Tyr also inhibited the RSV-induced shift of the unphosphorylated form I of IRF-3 to the phosphorylated form II. Pre-exposure of the cells to NO(2) (0.15 ppm, 4 h), which produced diffuse protein tyrosine nitration, did not affect RSV-induced release of RANTES, IL-8, or viral particles. NO2Tyr did not affect the potential of viral spreading to the neighboring cells since the RSV titers were not decreased when the uninfected cells were cocultured with the preinfected cells in NO2Tyr-containing medium. These results indicate that NO2Tyr, by replacing the COOH-terminal tyrosine of alpha-tubulin, attenuated RSV infection, and the inhibition appeared to occur at the early stages of RSV infection.

Topics: Antiviral Agents; Bronchi; Cell Line; Chemokine CCL5; DNA-Binding Proteins; Enzyme Inhibitors; Humans; Interferon Regulatory Factor-3; Interferon-gamma; Interleukin-8; Microtubules; Nitrogen; Nitrogen Dioxide; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Signal Transduction; Transcription Factors; Tubulin; Tumor Necrosis Factor-alpha; Tyrosine