title: Coal fly ash impairs airway antimicrobial peptides and increases bacterial growth.
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.
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Borcherding
authors.forename: Haihan
authors.initials: H
authors.lastname: Chen
authors.forename: Juan C
authors.initials: JC
authors.lastname: Caraballo
authors.forename: Jonas
authors.initials: J
authors.lastname: Baltrusaitis
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
authors.forename: Vicki H
authors.initials: VH
authors.lastname: Grassian
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Comellas
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001682:Biological Availability; D003031:Coal; D060729:Coal Ash / Q000737:chemistry / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007501:Iron / Q000032:analysis / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D003031:Coal; D060729:Coal Ash; D007501:Iron