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Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection.

Mikerov AN, Gan X, Umstead TM, Miller L, Chinchilli VM, Phelps DS, Floros J - Respir. Res. (2008)

Bottom Line: Sex differences have been described in a number of pulmonary diseases.Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h. 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice.Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. anm3@psu.edu

ABSTRACT

Background: Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with Klebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice.

Methods: Male and female C57BL/6 mice were exposed to O3 or to filtered air (FA) (control) and then infected intratracheally with K. pneumoniae bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h.

Results: 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice.

Conclusion: O3 exposure reduces the ability of mice to survive K. pneumoniae infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.

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Comparison of "cumulative" survival rates of males and females after ozone-exposure followed by K. pneumoniae infection. Experimental design was described in the legend for Figure 1, and in the Methods section. Panel A: Data (in percent of control – FA) for differences in survival between males and females. Panel B: Graphic representation of area below the curve (O3 and FA depicted by black and grey filled areas, respectively) of data shown in Panel A. The experiments from which these data are derived are in Panel B of Figure 1. The area below the curve was calculated with Sigma Plot 10.0 Software. O3 (top) and FA (bottom) curves. The resulting ratios (O3/FA times 100%) for males vs. females were compared with a t-test. Results were considered significant when p < 0.05, and are indicated with an asterisk, *.
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Figure 2: Comparison of "cumulative" survival rates of males and females after ozone-exposure followed by K. pneumoniae infection. Experimental design was described in the legend for Figure 1, and in the Methods section. Panel A: Data (in percent of control – FA) for differences in survival between males and females. Panel B: Graphic representation of area below the curve (O3 and FA depicted by black and grey filled areas, respectively) of data shown in Panel A. The experiments from which these data are derived are in Panel B of Figure 1. The area below the curve was calculated with Sigma Plot 10.0 Software. O3 (top) and FA (bottom) curves. The resulting ratios (O3/FA times 100%) for males vs. females were compared with a t-test. Results were considered significant when p < 0.05, and are indicated with an asterisk, *.

Mentions: Animals were anesthetized with an intramuscular injection of a mixture of Ketamine HCl (Ketaset, Fort Dodge Animal Health, IO) and Xylazine (XYLA-JECT, Phoenix Pharmacueticals Inc., St. Joseph, MO). The trachea was surgically exposed and ~450 CFU/mouse were inoculated intratracheally in 50 μl of PBS. Skin incision was closed with 7 mm wound clips. Deaths during the first 12 h post-infection period were considered to be due to surgical procedure rather than infection and those mice were excluded from study. Sixteen independent experiments (8 males and 8 females) were conducted. Each experiment consisted of 10 mice (5 exposed to FA or to O3). The mice were monitored for survival for 14 days. The total number of mice used for Figure 1 was 147 mice (75 FA-exposed [39 males+36 females]), and 72 O3-exposed [40 males + 32 females]). In cases (n = 14) where mice were moribund with no chance of recovery, these were euthanized to prevent unnecessary suffering according to Penn State University Institutional Animal Care and Use Committee recommendations and are included with the natural deaths. For the analysis shown in Figure 2, 130 mice were used out of the total 147 mice. Of these, 60 were males (6 independent experiments out 8) and 70 females (7 independent experiments out 8). Ratios from two experiments using males and from one with females were eliminated from analysis because the values measured were more than 2 standard deviations from the mean.


Sex differences in the impact of ozone on survival and alveolar macrophage function of mice after Klebsiella pneumoniae infection.

Mikerov AN, Gan X, Umstead TM, Miller L, Chinchilli VM, Phelps DS, Floros J - Respir. Res. (2008)

Comparison of "cumulative" survival rates of males and females after ozone-exposure followed by K. pneumoniae infection. Experimental design was described in the legend for Figure 1, and in the Methods section. Panel A: Data (in percent of control – FA) for differences in survival between males and females. Panel B: Graphic representation of area below the curve (O3 and FA depicted by black and grey filled areas, respectively) of data shown in Panel A. The experiments from which these data are derived are in Panel B of Figure 1. The area below the curve was calculated with Sigma Plot 10.0 Software. O3 (top) and FA (bottom) curves. The resulting ratios (O3/FA times 100%) for males vs. females were compared with a t-test. Results were considered significant when p < 0.05, and are indicated with an asterisk, *.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2268931&req=5

Figure 2: Comparison of "cumulative" survival rates of males and females after ozone-exposure followed by K. pneumoniae infection. Experimental design was described in the legend for Figure 1, and in the Methods section. Panel A: Data (in percent of control – FA) for differences in survival between males and females. Panel B: Graphic representation of area below the curve (O3 and FA depicted by black and grey filled areas, respectively) of data shown in Panel A. The experiments from which these data are derived are in Panel B of Figure 1. The area below the curve was calculated with Sigma Plot 10.0 Software. O3 (top) and FA (bottom) curves. The resulting ratios (O3/FA times 100%) for males vs. females were compared with a t-test. Results were considered significant when p < 0.05, and are indicated with an asterisk, *.
Mentions: Animals were anesthetized with an intramuscular injection of a mixture of Ketamine HCl (Ketaset, Fort Dodge Animal Health, IO) and Xylazine (XYLA-JECT, Phoenix Pharmacueticals Inc., St. Joseph, MO). The trachea was surgically exposed and ~450 CFU/mouse were inoculated intratracheally in 50 μl of PBS. Skin incision was closed with 7 mm wound clips. Deaths during the first 12 h post-infection period were considered to be due to surgical procedure rather than infection and those mice were excluded from study. Sixteen independent experiments (8 males and 8 females) were conducted. Each experiment consisted of 10 mice (5 exposed to FA or to O3). The mice were monitored for survival for 14 days. The total number of mice used for Figure 1 was 147 mice (75 FA-exposed [39 males+36 females]), and 72 O3-exposed [40 males + 32 females]). In cases (n = 14) where mice were moribund with no chance of recovery, these were euthanized to prevent unnecessary suffering according to Penn State University Institutional Animal Care and Use Committee recommendations and are included with the natural deaths. For the analysis shown in Figure 2, 130 mice were used out of the total 147 mice. Of these, 60 were males (6 independent experiments out 8) and 70 females (7 independent experiments out 8). Ratios from two experiments using males and from one with females were eliminated from analysis because the values measured were more than 2 standard deviations from the mean.

Bottom Line: Sex differences have been described in a number of pulmonary diseases.Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h. 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice.Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. anm3@psu.edu

ABSTRACT

Background: Sex differences have been described in a number of pulmonary diseases. However, the impact of ozone exposure followed by pneumonia infection on sex-related survival and macrophage function have not been reported. The purpose of this study was to determine whether ozone exposure differentially affects: 1) survival of male and female mice infected with Klebsiella pneumoniae, and 2) the phagocytic ability of macrophages from these mice.

Methods: Male and female C57BL/6 mice were exposed to O3 or to filtered air (FA) (control) and then infected intratracheally with K. pneumoniae bacteria. Survival was monitored over a 14-day period, and the ability of alveolar macrophages to phagocytize the pathogen in vivo was investigated after 1 h.

Results: 1) Both male and female mice exposed to O3 are significantly more susceptible to K. pneumoniae infection than mice treated with FA; 2) although females appeared to be more resistant to K. pneumoniae than males, O3 exposure significantly increased the susceptibility of females to K. pneumoniae infection to a greater degree than males; 3) alveolar macrophages from O3-exposed male and female mice have impaired phagocytic ability compared to macrophages from FA-exposed mice; and 4) the O3-dependent reduction in phagocytic ability is greater in female mice.

Conclusion: O3 exposure reduces the ability of mice to survive K. pneumoniae infection and the reduced phagocytic ability of alveolar macrophages may be one of the contributing factors. Both events are significantly more pronounced in female mice following exposure to the environmental pollutant, ozone.

Show MeSH
Related in: MedlinePlus