Residual oil fly ash and charged polymers activate epithelial cells and nociceptive sensory neurons

Residual oil fly ash (ROFA) is an industrial pollutant that contains metals , acids, and unknown materials complexed to a particulate core. The heterog eneous composition of ROFA hampers finding the mechanism(s) by which it and other particulate pollutants cause airway toxicity. To distinguish culpabl e factors contributing to the effects of ROFA, synthetic polymer microspher e (SPM) analogs were synthesized that resembled ROFA in particle size (2 an d 6 mu m in diameter) and zeta potential (-29 mV). BEAS-2B human bronchial epithelial cells and dorsal root ganglion neurons responded to both ROFA an d charged SPMs with an increase in intracellular Ca2+ concentration ([Ca2+] (i)) and the release of the proinflammatory cytokine interleukin-6, whereas neutral SPMs bound with polyethylene glycol (0-mV zeta potential) were rel atively ineffective. In dorsal root ganglion neurons, the SPM-induced incre ases in [Ca2+](i) were correlated with the presence of acid- and/or capsaic in-sensitive pathways. We hypothesized that the acidic microenvironment ass ociated with negatively charged colloids like ROFA and SPMs activate irrita nt receptors in airway target cells. This causes subsequent cytokine releas e, which mediates the pathophysiology of neurogenic airway inflammation.