Abstract
BackgroundSurfactant protein A (SP-A) enhances phagocytosis of bacteria, including Klebsiella pneumoniae, by alveolar macrophages. Ozone, a major air pollutant, can cause oxidation of surfactant and may influence lung immune function. Immune function may also be affected by sex-specific mechanisms. We hypothesized that ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure, and that sex differences in the effect of ozone do exist.MethodsMale and female SP-A (-/-) mice on the C57BL/6J background were exposed to ozone or to filtered air (FA) used as a control and then infected intratracheally with K. pneumoniae bacteria. Survival rate was monitored during a 14-day period. In addition, protein oxidation levels and in vivo phagocytosis were checked 1 h after inoculation of PBS used as a sham control and after inoculation of K. pneumoniae bacteria in PBS, respectively.ResultsWe found: 1) ozone exposure followed by K. pneumoniae infection decreases survival and alveolar macrophage phagocytic function of SP-A (-/-) mice compared to filtered air exposure (p < 0.05), and females are more affected than males; 2) SP-A (-/-) mice (exposed either to ozone or FA) are more susceptible to infection with K. pneumoniae than wild type (WT) mice regarding their survival rate and macrophage phagocytic function; the phagocytic function of FA SP-A(-/-) is similar to that of ozone exposed WT. 3) ozone exposure appears to increase infiltration of PMNs, total protein, and SP-A oxidation in WT mice; infiltration of PMNs and total protein oxidation appears to be more pronounced in female mice in response to ozone; 4) ozone exposure increases SP-A oxidation in WT females significantly more than in males.ConclusionAbsence (i.e. ablation of SP-A in SP-A (-/-) mice) or reduction of functional activity of SP-A (i.e. oxidation of SP-A in WT mice) increases the susceptibility of mice to experimental pneumonia after ozone exposure, and in both cases females are more affected by ozone exposure than males.
Highlights
Surfactant protein A (SP-A) enhances phagocytosis of bacteria, including Klebsiella pneumoniae, by alveolar macrophages
Effect of ozone-exposure on survival of SP-A (-/-) mice after K. pneumoniae infection In this part of the study, we investigated the following hypotheses: i) ozone exposure affects the ability of SP-A (/-) mice to survive after K. pneumoniae infection, and ii) female mice have a higher risk for pneumonia due to infection with K. pneumoniae after ozone exposure than males
We first exposed mice to ozone and infected them with K. pneumoniae bacteria
Summary
Surfactant protein A (SP-A) enhances phagocytosis of bacteria, including Klebsiella pneumoniae, by alveolar macrophages. A major air pollutant, can cause oxidation of surfactant and may influence lung immune function. We hypothesized that ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure, and that sex differences in the effect of ozone do exist. Millions of Americans live in areas with a level of ozone higher than that recommended by the National Ambient Air Quality Standard limit, and this could negatively affect their health. Ozone exposure can cause shortness of breath and coughing, trigger asthma attacks and reduce lung function, often leading to hospital admissions and emergency room visits [1,2,3,4]. Pneumonia and influenza cost the U.S economy more than $40.2 billion in 2005, according to the American Lung Association
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