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Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

Borcherding JA, Chen H, Caraballo JC, Baltrusaitis J, Pezzulo AA, Zabner J, Grassian VH, Comellas AP - PLoS ONE (2013)

Bottom Line: Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results.CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects.CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.

ABSTRACT
Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

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Related in: MedlinePlus

CFA increases bacterial grown in vivo.Panel A. Total mouse lung sterility in vivo. After 24 hours, CFUs were determined after homogenizing lungs and plating to determine growth. In the presence of CFA, lung sterility was decreased by 20–30% **p<0.01, ***p<0.0001. PA01 alone N = 26, PA01+ FA 2689 N = 22, PA01+ FA 2690 N = 21, and PA01+ FA 2691 N = 24. Panel B. Growth in non-sterile mice. Log CFU/mouse was determined. FA 2689 and FA 2690 increased growth more than control (p<0.05).
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pone-0057673-g001: CFA increases bacterial grown in vivo.Panel A. Total mouse lung sterility in vivo. After 24 hours, CFUs were determined after homogenizing lungs and plating to determine growth. In the presence of CFA, lung sterility was decreased by 20–30% **p<0.01, ***p<0.0001. PA01 alone N = 26, PA01+ FA 2689 N = 22, PA01+ FA 2690 N = 21, and PA01+ FA 2691 N = 24. Panel B. Growth in non-sterile mice. Log CFU/mouse was determined. FA 2689 and FA 2690 increased growth more than control (p<0.05).

Mentions: Data are presented as means ± SEM. The program used for data analysis was GraphPad Prism 5.00 (San Diego, CA). The following information provides the analysis method for each figure and panel. Fisher’s analysis of a contingency table of sterility was used to determine significance in Figure 1A. In Figures 1B and 2A–D, One-way ANOVA using Dunnett’s Multiple Comparison Test was used. Figure 3A, Fisher’s analysis of a contingency table of sterility was used to determine significance. Figures 3B–C and Figures 4A–B, One-way ANOVA using Dunnett’s Multiple Comparison Test was used to determine significance. In Figure 5, non-linear regression (curve-fit) with variable slope from three independent experiments was used for statistical analysis. Data was compared for all parameters of the growth curve using the extra sum of squares F-test to detect differences throughout the entire growth curve. A p value of <0.05 was considered statistically significant.


Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.

Borcherding JA, Chen H, Caraballo JC, Baltrusaitis J, Pezzulo AA, Zabner J, Grassian VH, Comellas AP - PLoS ONE (2013)

CFA increases bacterial grown in vivo.Panel A. Total mouse lung sterility in vivo. After 24 hours, CFUs were determined after homogenizing lungs and plating to determine growth. In the presence of CFA, lung sterility was decreased by 20–30% **p<0.01, ***p<0.0001. PA01 alone N = 26, PA01+ FA 2689 N = 22, PA01+ FA 2690 N = 21, and PA01+ FA 2691 N = 24. Panel B. Growth in non-sterile mice. Log CFU/mouse was determined. FA 2689 and FA 2690 increased growth more than control (p<0.05).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585163&req=5

pone-0057673-g001: CFA increases bacterial grown in vivo.Panel A. Total mouse lung sterility in vivo. After 24 hours, CFUs were determined after homogenizing lungs and plating to determine growth. In the presence of CFA, lung sterility was decreased by 20–30% **p<0.01, ***p<0.0001. PA01 alone N = 26, PA01+ FA 2689 N = 22, PA01+ FA 2690 N = 21, and PA01+ FA 2691 N = 24. Panel B. Growth in non-sterile mice. Log CFU/mouse was determined. FA 2689 and FA 2690 increased growth more than control (p<0.05).
Mentions: Data are presented as means ± SEM. The program used for data analysis was GraphPad Prism 5.00 (San Diego, CA). The following information provides the analysis method for each figure and panel. Fisher’s analysis of a contingency table of sterility was used to determine significance in Figure 1A. In Figures 1B and 2A–D, One-way ANOVA using Dunnett’s Multiple Comparison Test was used. Figure 3A, Fisher’s analysis of a contingency table of sterility was used to determine significance. Figures 3B–C and Figures 4A–B, One-way ANOVA using Dunnett’s Multiple Comparison Test was used to determine significance. In Figure 5, non-linear regression (curve-fit) with variable slope from three independent experiments was used for statistical analysis. Data was compared for all parameters of the growth curve using the extra sum of squares F-test to detect differences throughout the entire growth curve. A p value of <0.05 was considered statistically significant.

Bottom Line: Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results.CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects.CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.

ABSTRACT
Air pollution is a risk factor for respiratory infections, and one of its main components is particulate matter (PM), which is comprised of a number of particles that contain iron, such as coal fly ash (CFA). Since free iron concentrations are extremely low in airway surface liquid (ASL), we hypothesize that CFA impairs antimicrobial peptides (AMP) function and can be a source of iron to bacteria. We tested this hypothesis in vivo by instilling mice with Pseudomonas aeruginosa (PA01) and CFA and determine the percentage of bacterial clearance. In addition, we tested bacterial clearance in cell culture by exposing primary human airway epithelial cells to PA01 and CFA and determining the AMP activity and bacterial growth in vitro. We report that CFA is a bioavailable source of iron for bacteria. We show that CFA interferes with bacterial clearance in vivo and in primary human airway epithelial cultures. Also, we demonstrate that CFA inhibits AMP activity in vitro, which we propose as a mechanism of our cell culture and in vivo results. Furthermore, PA01 uses CFA as an iron source with a direct correlation between CFA iron dissolution and bacterial growth. CFA concentrations used are very relevant to human daily exposures, thus posing a potential public health risk for susceptible subjects. Although CFA provides a source of bioavailable iron for bacteria, not all CFA particles have the same biological effects, and their propensity for iron dissolution is an important factor. CFA impairs lung innate immune mechanisms of bacterial clearance, specifically AMP activity. We expect that identifying the PM mechanisms of respiratory infections will translate into public health policies aimed at controlling, not only concentration of PM exposure, but physicochemical characteristics that will potentially cause respiratory infections in susceptible individuals and populations.

Show MeSH
Related in: MedlinePlus