title: Residual oil fly ash and charged polymers activate epithelial cells and nociceptive sensory neurons.
abstract: Residual oil fly ash (ROFA) is an industrial pollutant that contains metals, acids, and unknown materials complexed to a particulate core. The heterogeneous composition of ROFA hampers finding the mechanism(s) by which it and other particulate pollutants cause airway toxicity. To distinguish culpable factors contributing to the effects of ROFA, synthetic polymer microsphere (SPM) analogs were synthesized that resembled ROFA in particle size (2 and 6 microm in diameter) and zeta potential (-29 mV). BEAS-2B human bronchial epithelial cells and dorsal root ganglion neurons responded to both ROFA and charged SPMs with an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) and the release of the proinflammatory cytokine interleukin-6, whereas neutral SPMs bound with polyethylene glycol (0-mV zeta potential) were relatively ineffective. In dorsal root ganglion neurons, the SPM-induced increases in [Ca(2+)](i) were correlated with the presence of acid- and/or capsaicin-sensitive pathways. We hypothesized that the acidic microenvironment associated with negatively charged colloids like ROFA and SPMs activate irritant receptors in airway target cells. This causes subsequent cytokine release, which mediates the pathophysiology of neurogenic airway inflammation.
authors.affiliation: Departments of Anesthesiology and Neurobiology, Duke University marga@neuro.duke.edu
authors.forename: M
authors.initials: M
authors.lastname: Oortgiesen
authors.forename: B
authors.initials: B
authors.lastname: Veronesi
authors.forename: G
authors.initials: G
authors.lastname: Eichenbaum
authors.forename: P F
authors.initials: PF
authors.lastname: Kiser
authors.forename: S A
authors.initials: SA
authors.lastname: Simon
mesh_terms: D000143:Acids / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002244:Carbon / Q000494:pharmacology*; D060729:Coal Ash; D004563:Electrochemistry; D004847:Epithelial Cells / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008863:Microspheres; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D009994:Osmolar Concentration; D052638:Particulate Matter; D011092:Polyethylene Glycols / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000143:Acids; D060729:Coal Ash; D015850:Interleukin-6; D052638:Particulate Matter; D011108:Polymers; D011092:Polyethylene Glycols; D002244:Carbon; D002211:Capsaicin; D002118:Calcium