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Ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure: sex differences.

Mikerov AN, Haque R, Gan X, Guo X, Phelps DS, Floros J - Respir. Res. (2008)

Bottom Line: 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.We 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.Absence (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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Penn State Center for Host defense, Inflammation, and Lung Disease Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. a_mikerov@mail.ru

ABSTRACT

Background: Surfactant 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.

Methods: Male 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.

Results: We 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.

Conclusion: Absence (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.

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Net effect of ozone exposure on total protein oxidation and SP-A oxidation in BAL of WT male and female mice. The data for ozone-exposed mice are from Figures 6B and 7B and they were normalized to the control (FA) that was set equal to 100%. The average of OD × mm2 for FA-exposed mice (control) was calculated for each experiment (n = 4). The net effect of ozone on total protein oxidation and SP-A oxidation in mouse BAL was calculated according to the following formula: OD × mm2 for each ozone-exposed mouse/OD × mm2 of the average for the FA-exposed mice from the same experiment, times 100%. Significant differences are shown with lines above the respective bars. Data were considered as significant if p < 0.05 with a t-test.
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Figure 8: Net effect of ozone exposure on total protein oxidation and SP-A oxidation in BAL of WT male and female mice. The data for ozone-exposed mice are from Figures 6B and 7B and they were normalized to the control (FA) that was set equal to 100%. The average of OD × mm2 for FA-exposed mice (control) was calculated for each experiment (n = 4). The net effect of ozone on total protein oxidation and SP-A oxidation in mouse BAL was calculated according to the following formula: OD × mm2 for each ozone-exposed mouse/OD × mm2 of the average for the FA-exposed mice from the same experiment, times 100%. Significant differences are shown with lines above the respective bars. Data were considered as significant if p < 0.05 with a t-test.

Mentions: Total protein concentration was significantly increased in the BAL from males in response to ozone, as we showed before [42], but no significant difference was observed in samples from female mice (Figure 6A). Total protein oxidation appeared to be increased (albeit not significantly) in BAL of ozone-exposed mice with females showing a smaller but significant increase in the levels of oxidized protein in BAL compared to males (Figure 6B). Analysis of the total SP-A (monomer, dimer, and both) demonstrated that SP-A concentration in BAL appeared to increase in response to ozone, and that the values from females were higher than those from males (p < 0.05) for all monomer, dimer, and total SP-A for ozone-exposed mice (Figure 7A). Oxidized SP-A dimer analysis (only dimer was found to be oxidized in mouse SP-A) revealed that ozone increased the oxidation of SP-A dimer (with p < 0.05 for females only) (Figure 7B and 7C). To assess the net effect of ozone on the total protein oxidation and SP-A oxidation in mouse BAL, the percent of ozone/FA values were calculated. The analysis revealed that ozone appeared to increase oxidation of the total protein in BAL, albeit not significantly. However, ozone specifically increased oxidation of SP-A (p < 0.05 for females only) with female mice showing a significantly (p < 0.05) higher level of SP-A oxidation than males (Figure 8).


Ablation of SP-A has a negative impact on the susceptibility of mice to Klebsiella pneumoniae infection after ozone exposure: sex differences.

Mikerov AN, Haque R, Gan X, Guo X, Phelps DS, Floros J - Respir. Res. (2008)

Net effect of ozone exposure on total protein oxidation and SP-A oxidation in BAL of WT male and female mice. The data for ozone-exposed mice are from Figures 6B and 7B and they were normalized to the control (FA) that was set equal to 100%. The average of OD × mm2 for FA-exposed mice (control) was calculated for each experiment (n = 4). The net effect of ozone on total protein oxidation and SP-A oxidation in mouse BAL was calculated according to the following formula: OD × mm2 for each ozone-exposed mouse/OD × mm2 of the average for the FA-exposed mice from the same experiment, times 100%. Significant differences are shown with lines above the respective bars. Data were considered as significant if p < 0.05 with a t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 8: Net effect of ozone exposure on total protein oxidation and SP-A oxidation in BAL of WT male and female mice. The data for ozone-exposed mice are from Figures 6B and 7B and they were normalized to the control (FA) that was set equal to 100%. The average of OD × mm2 for FA-exposed mice (control) was calculated for each experiment (n = 4). The net effect of ozone on total protein oxidation and SP-A oxidation in mouse BAL was calculated according to the following formula: OD × mm2 for each ozone-exposed mouse/OD × mm2 of the average for the FA-exposed mice from the same experiment, times 100%. Significant differences are shown with lines above the respective bars. Data were considered as significant if p < 0.05 with a t-test.
Mentions: Total protein concentration was significantly increased in the BAL from males in response to ozone, as we showed before [42], but no significant difference was observed in samples from female mice (Figure 6A). Total protein oxidation appeared to be increased (albeit not significantly) in BAL of ozone-exposed mice with females showing a smaller but significant increase in the levels of oxidized protein in BAL compared to males (Figure 6B). Analysis of the total SP-A (monomer, dimer, and both) demonstrated that SP-A concentration in BAL appeared to increase in response to ozone, and that the values from females were higher than those from males (p < 0.05) for all monomer, dimer, and total SP-A for ozone-exposed mice (Figure 7A). Oxidized SP-A dimer analysis (only dimer was found to be oxidized in mouse SP-A) revealed that ozone increased the oxidation of SP-A dimer (with p < 0.05 for females only) (Figure 7B and 7C). To assess the net effect of ozone on the total protein oxidation and SP-A oxidation in mouse BAL, the percent of ozone/FA values were calculated. The analysis revealed that ozone appeared to increase oxidation of the total protein in BAL, albeit not significantly. However, ozone specifically increased oxidation of SP-A (p < 0.05 for females only) with female mice showing a significantly (p < 0.05) higher level of SP-A oxidation than males (Figure 8).

Bottom Line: 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.We 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.Absence (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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Penn State Center for Host defense, Inflammation, and Lung Disease Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. a_mikerov@mail.ru

ABSTRACT

Background: Surfactant 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.

Methods: Male 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.

Results: We 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.

Conclusion: Absence (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.

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Related in: MedlinePlus