Effects of subchronic exposure to a mixture of O₃, SO₂, and (NH₄)₂SO₄on host defenses of mice

Abstract

Mice exposed 5 h/d, 5 d/wk up to 103 d, to 0.2 mg O3/m3 or to a mixture of O3, 13.2 mg SO2/m3, and 1.04 mg (NH4)2SO4 aerosol/m3 showed significantly greater susceptibility to group C streptococcal aerosol infection relative to filtered air controls. Pulmonary bactericidal activity by alveolar macrophages was significantly enhanced in the lungs of mice exposed to the mixture relative to those inhaling filtered air or O3 alone. The total number and distribution of the free cells lavaged from the lungs, as well as cellular ATP levels, did not change due to the pollutant exposures. In vitro cytostasis in tumor target cells cocultured with peritoneal macrophages from the exposed mice was significantly enhanced in the O3-exposed and in the mixture-exposed treatment groups relative to controls and also in the mixture-exposed relative to the O3-exposed group when a target-to-effector-cell ratio of 1:10 was used; no such effects were observed when this ratio was 1:20. Splenic T-lymphocyte function, as measured by blastogenesis to mitogens and alloantigens, was affected by exposure to O3 and/or the mixture, although the patterns of effects were qualitatively different. Splenic B-cell function and macrophage antigen processing, as measured by the generation of antibody plaque-forming cells, was unaffected by exposure.

Ambient Ozone Primes Pulmonary Innate Immunity in Mice

“…In this study, we have demonstrated that ozone can substantially affect the response to LPS by priming the innate immune system through TLR4 cell surface expression. These findings are entirely consistent with the observed effect of ozone on decreased clearance of live bacterial pathogens (12,(17)(18)(19)(20)(21). Moreover, these findings provide a biological hypothesis for the epidemiological relationship between ozone and increased pulmonary morbidity and mortality.…”

“…However, COPD is characterized by increased numbers of macrophages, neutrophils, and cytotoxic CD8 lymphocytes, suggesting a role of innate immune function in pathogenesis of this disease. Ozone is known to alter macrophage function (12,13). Alveolar macrophages exposed to ozone in vitro demonstrate reduced phagocytosis in both rodents (14) and humans (15), which in part is related to cytotoxicity (16).…”

“…Alveolar macrophages exposed to ozone in vitro demonstrate reduced phagocytosis in both rodents (14) and humans (15), which in part is related to cytotoxicity (16). In addition, exposure to ozone is associated with impaired clearance of multiple live organisms, including the following: Streptococcus zooepidemicus (17), Streptococcus pyogenes (12), Staphylococcus aureus (18), Klebsiella pneumonia (19), Mycobacteria tuberculosis (20), and Listeria monocytogenes (21). Altered vulnerability to these bacterial pathogens suggests that ozone could specifically impair innate immune function in the lung and provide an underlying mechanism for the enhanced morbidity and mortality observed in human populations exposed to higher concentrations of ambient ozone.…”

Effects of inhaled acids on respiratory tract defense mechanisms.

“…However, Aranyi et al (52) found no change in total or differential counts of free cells lavaged from mice exposed to (NH4)2SO4 at 1 mg/m3 for 3 hr/day for 20 days; this suggests a lack of inflammatory response to this sulfate aerosol. A study in our laboratory (59) is examining early alveolar clearance in rabbits at various time intervals during the course of a series of intermittent (1 hr/day, 5 days/week) exposures to submicrometer H2SO4 at 0.25 mg/im3.…”

Ozone Enhances Pulmonary Innate Immune Response to a Toll-Like Receptor–2 Agonist

“…A number of studies in animals suggested that preexposure to ozone exerts an influence on pulmonary host defense. Exposure to ozone was associated with the impaired clearance of several bacteria, including Klebsiella pneumoniae (15), Listeria monocytogenes (16), Mycobacterium tuberculosis (17), Staphylococcus aureus (18), Streptococcus pyogenes (19), and Streptococcus zooepidemicus (20). This impairment in antibacterial host defense is at least in part explained by the disruption of the epithelial barrier and the inefficiency of phagocytosis.…”