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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 (10 µg/mL) in the presence of PA01 does not significantly increase neutrophil recruitment or cytokine production in BAL.Panel A. When C57/Bl6 mice were exposed to 10 µg/mL CFA in the presence and absence of PA01 (4.5 106 PA01/mouse), total BAL cell count was not significantly different between Ct and PA01 but there was an increase in neutrophil percentage in the presence of PA01. However, there were no significant cell count differences between PA01 and PA01 with FA2690. Panel B. Although neutrophil recruitment in mice BAL was higher, there was no statistically significant difference between control and PA01 nor PA01 and PA01 with FA2690. Panel C. IL-1β in the presence of PA01 and CFA increased production more than PA01 alone but was not significantly different. Panel D. TNF-α in the presence of PA01 and CFA does not significantly increase compared with PA01 alone. N = 5.
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pone-0057673-g002: CFA (10 µg/mL) in the presence of PA01 does not significantly increase neutrophil recruitment or cytokine production in BAL.Panel A. When C57/Bl6 mice were exposed to 10 µg/mL CFA in the presence and absence of PA01 (4.5 106 PA01/mouse), total BAL cell count was not significantly different between Ct and PA01 but there was an increase in neutrophil percentage in the presence of PA01. However, there were no significant cell count differences between PA01 and PA01 with FA2690. Panel B. Although neutrophil recruitment in mice BAL was higher, there was no statistically significant difference between control and PA01 nor PA01 and PA01 with FA2690. Panel C. IL-1β in the presence of PA01 and CFA increased production more than PA01 alone but was not significantly different. Panel D. TNF-α in the presence of PA01 and CFA does not significantly increase compared with PA01 alone. N = 5.

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 (10 µg/mL) in the presence of PA01 does not significantly increase neutrophil recruitment or cytokine production in BAL.Panel A. When C57/Bl6 mice were exposed to 10 µg/mL CFA in the presence and absence of PA01 (4.5 106 PA01/mouse), total BAL cell count was not significantly different between Ct and PA01 but there was an increase in neutrophil percentage in the presence of PA01. However, there were no significant cell count differences between PA01 and PA01 with FA2690. Panel B. Although neutrophil recruitment in mice BAL was higher, there was no statistically significant difference between control and PA01 nor PA01 and PA01 with FA2690. Panel C. IL-1β in the presence of PA01 and CFA increased production more than PA01 alone but was not significantly different. Panel D. TNF-α in the presence of PA01 and CFA does not significantly increase compared with PA01 alone. N = 5.
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Related In: Results  -  Collection

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

pone-0057673-g002: CFA (10 µg/mL) in the presence of PA01 does not significantly increase neutrophil recruitment or cytokine production in BAL.Panel A. When C57/Bl6 mice were exposed to 10 µg/mL CFA in the presence and absence of PA01 (4.5 106 PA01/mouse), total BAL cell count was not significantly different between Ct and PA01 but there was an increase in neutrophil percentage in the presence of PA01. However, there were no significant cell count differences between PA01 and PA01 with FA2690. Panel B. Although neutrophil recruitment in mice BAL was higher, there was no statistically significant difference between control and PA01 nor PA01 and PA01 with FA2690. Panel C. IL-1β in the presence of PA01 and CFA increased production more than PA01 alone but was not significantly different. Panel D. TNF-α in the presence of PA01 and CFA does not significantly increase compared with PA01 alone. N = 5.
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