Working hypothesis on the mechanism of the synergic adverse effects of ambient ozone and PM2.5 particulates

Abstract

The pulmonary epithelium is protected against atm. ozone O_3(g) by a fluid film (ELF) contg. ascorbic acid (AH2) and related antioxidants. This mechanism of protection however fails if co-pollutants redirect AH_2 and O_3(g) into species that can transduce oxidative damage to underlying tissues. We have shown (Enami et al., PNAS 2008) that, whereas the ozonation of ascorbate AH-[pK_a(AH_2) = 4.1] under physiol. conditions yields innocuous dehydroascorbic acid, the ozonation of AH_2 in pH < 5 acidic media generates a cytotoxic ozonide. On this basis we speculated that acidic particulates, by acidifying ELF below its normal pH = 6.9 value, would disable its protective antioxidant function. Here we refine our proposal by showing that the typical buffer capacities of ELF's (∼ 10 mM/pH) prevent their direct (chem.) acidification by the inhalation of polluted ambient air contg. representative acidic particulate loadings (< 100 mg/m^3). We propose instead, on the basis of extensive clin. and physiol. studies on the innate lung host defense response, that ELF acidification is mediated by inflammatory reaction to acidic particulates. On this basis, ultrafine particulates, which reach the alveoli whose ELF is ∼ 50 times thinner than that of the airways, are expected to be pose a particularly aggressive challenge to underlying alveolar macrophages.

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