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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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Differential cell counts in BAL of FA-exposed and ozone-exposed WT male and female mice. Experimental design was as described for in vivo phagocytosis (Figure 4), except that PBS was injected into mice instead of bacteria (see Methods). The percent of polymorphonuclear neutrophils (PMNs), lymphocytes, and macrophages/monocytes was calculated and compared between ozone-exposed and FA-exposed mice and between males and females. The percent of lymphocytes did not differ significantly among different groups. The number of mice in this analysis is shown in the Figure. The number of independent experiments was 4, where each experiment initially involved 6 mice (3 FA-exposed mice and 3 ozone-exposed). Significant differences are shown with lines above the respective bars. Statistical analysis was performed with a t-test and the differences were considered significant if p < 0.05.
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Figure 5: Differential cell counts in BAL of FA-exposed and ozone-exposed WT male and female mice. Experimental design was as described for in vivo phagocytosis (Figure 4), except that PBS was injected into mice instead of bacteria (see Methods). The percent of polymorphonuclear neutrophils (PMNs), lymphocytes, and macrophages/monocytes was calculated and compared between ozone-exposed and FA-exposed mice and between males and females. The percent of lymphocytes did not differ significantly among different groups. The number of mice in this analysis is shown in the Figure. The number of independent experiments was 4, where each experiment initially involved 6 mice (3 FA-exposed mice and 3 ozone-exposed). Significant differences are shown with lines above the respective bars. Statistical analysis was performed with a t-test and the differences were considered significant if p < 0.05.

Mentions: For the counting of total cells in whole BAL, no significant differences were found between males and females or between ozone-exposed and FA-exposed mouse BALs (data not shown). Differential cell counting revealed an increased number of PMNs in BAL in response to ozone (it was significant only for males), as we have observed before [42]. Moreover, females appeared to be more sensitive to experimental stress than males. They increased the number of PMNs in response to both FA (p < 0.05) and ozone (albeit non-significantly) compared to males (Figure 5). The number of macrophages was changed accordingly in the differential cell counts (Figure 5). In addition, the number of PMNs or macrophages from ozone-exposed males was similar to that of FA-exposed females (Figure 5).


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)

Differential cell counts in BAL of FA-exposed and ozone-exposed WT male and female mice. Experimental design was as described for in vivo phagocytosis (Figure 4), except that PBS was injected into mice instead of bacteria (see Methods). The percent of polymorphonuclear neutrophils (PMNs), lymphocytes, and macrophages/monocytes was calculated and compared between ozone-exposed and FA-exposed mice and between males and females. The percent of lymphocytes did not differ significantly among different groups. The number of mice in this analysis is shown in the Figure. The number of independent experiments was 4, where each experiment initially involved 6 mice (3 FA-exposed mice and 3 ozone-exposed). Significant differences are shown with lines above the respective bars. Statistical analysis was performed with a t-test and the differences were considered significant if p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2655296&req=5

Figure 5: Differential cell counts in BAL of FA-exposed and ozone-exposed WT male and female mice. Experimental design was as described for in vivo phagocytosis (Figure 4), except that PBS was injected into mice instead of bacteria (see Methods). The percent of polymorphonuclear neutrophils (PMNs), lymphocytes, and macrophages/monocytes was calculated and compared between ozone-exposed and FA-exposed mice and between males and females. The percent of lymphocytes did not differ significantly among different groups. The number of mice in this analysis is shown in the Figure. The number of independent experiments was 4, where each experiment initially involved 6 mice (3 FA-exposed mice and 3 ozone-exposed). Significant differences are shown with lines above the respective bars. Statistical analysis was performed with a t-test and the differences were considered significant if p < 0.05.
Mentions: For the counting of total cells in whole BAL, no significant differences were found between males and females or between ozone-exposed and FA-exposed mouse BALs (data not shown). Differential cell counting revealed an increased number of PMNs in BAL in response to ozone (it was significant only for males), as we have observed before [42]. Moreover, females appeared to be more sensitive to experimental stress than males. They increased the number of PMNs in response to both FA (p < 0.05) and ozone (albeit non-significantly) compared to males (Figure 5). The number of macrophages was changed accordingly in the differential cell counts (Figure 5). In addition, the number of PMNs or macrophages from ozone-exposed males was similar to that of FA-exposed females (Figure 5).

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