Our previous results from CAPs exposure studies in Detroit suggest that exacerbation of allergic airway inflammation is associated with PM2.5 primarily associated with sewage sludge incineration, refineries, and secondary sulfate/coal-combustion utilities rather than from diesel- or gasoline-powered motor vehicles [15, 16]. In the present study we again found PM2.5 -induced enhancement of allergic airway responses at our Detroit exposure site, but in contrast we also document inhibitory results by inhalation of Grand Rapids PM2.5 despite using the same exposure and treatment protocols and similar CAP mass concentrations (519 μg/m3 vs 542 μg/m3; Grand Rapids and Detroit, respectively). Because these divergent responses are independent of PM2.5 mass, then specific physicochemical attributes of the exposure aerosols must be driving the inhibition (Grand Rapids) and enhancement (Detroit) of allergic airway responses.
During the 8-h exposure period in Detroit southerly winds, associated with a high-pressure system centered over the Ohio River Valley, brought humid air masses and elevated levels of the transported or secondary particles dominated by sulfates to the exposure site. In addition to secondary/transported sulfate, increased concentrations of anthropogenic metals including Pb, V, and Se, suggest that the site was also impacted by emissions from the local industrial sources that we have identified southwest of the exposure study location. The potential combination of sulfates and metals to exacerbate allergic responses is consistent with results from a comparison study of PM2.5 collected from two German communities , which showed that PM samples with higher sulfates, Pb and other metals were more potent airway inflammagens in both allergic and normal mice. In another comparison study of PM2.5 collected from several European cities, the potency of PM to elicit immune response in mice was associated with V, Ni, and SO4 content of particles .
In contrast to the Detroit exposure, the dominant wind direction during the 8-h exposure period in Grand Rapids was northerly, bringing relatively clean air since there are few major emission sources in that direction. Temporal variations of NOx, CO and SO2 concentrations indicated a strong impact from the traffic in the morning. Therefore our observations for inhibition of eosinophil and mucus responses by Grand Rapids CAPs runs counter to epidemiological findings for traffic-associated asthma symptoms and hospitals visits [32–34]. These reported associations were specific for children, and asthma diagnoses were derived from pulmonary function endpoints and not from inflammatory cell infiltration and mucus production that we describe in rats. Results from animal models of allergic airways disease have reported both positive and negative correlations of airway inflammation (i.e., BALF cellularity) with altered airway function [35, 36]. Another key difference is that our study addressed the effects of a single exposure to PM during the initial antigen challenge compared to chronic exposures of children to the daily variations of urban traffic, PM and allergens.
In past studies with multiple CAPs exposures (3–13 days) we have documented both enhancement, as well as no effects on allergic inflammatory responses in rats [14, 17]. It was often challenging to decipher which exposure day had the most impact during those multi-day studies. The present comparison provides much clearer and distinct exposure profiles, as well as their opposing biological effects in animals.
Our results with Grand Rapids CAPs are reminiscent of our recent findings using the same Brown Norway –ovalbumin protocols where we used inhalation exposure to diesel engine exhaust (DEE) instead of CAPs. Inhalation of as little as 30 μg/m3 DEE also inhibited allergic airway inflammation and mucous cell metaplasia in asthmatic rats . Components of diesel fuel emissions can induce Phase II enzymes in B-lymphocytes and inhibit IgE production . We detected a decrease in OVA-specific IgE in serum of allergic rats exposed to Grand Rapids CAPs compared to allergic rats exposed to filtered air. These data are not shown because we did not conduct a similar analysis in Detroit to make a meaningful comparison. Several examples in airway cell culture systems suggest that PM2.5 -mediated depression of immune and inflammatory responses may be associated with oxidant capacity and toll-like receptor (TLR) activation [38–40]. These observations include inhibition of cytokine release or mediator production from airway epithelium or mononuclear inflammatory cells. Endotoxin from gram-negative bacteria, a TLR4 activator, can inhibit allergic inflammation during allergen challenge in ovalbumin-rat protocols . We did not analyze PM samples for endotoxins in either Detroit or Grand Rapids, so it is possible that biogenic substances such as endotoxins may be present in PM where they contribute to inhibition of allergic responses.
Another notable difference between the exposures was that smaller size fractions of PM2.5 (<PM0.6) and ultrafine fraction (<PM0.18) was more than twice as high in Detroit CAPs compared to Grand Rapids. This finding suggests that impacts from local Detroit combustion sources were greater than from Grand Rapids. While the increased ultrafine concentrations could not be directly associated with the observed health effects in the present study, other studies have shown the size fraction may play an important role in understanding the PM health effects. For example, our recent study in Los Angeles suggests that ultrafine PM (100 μg/m3) can exacerbate allergic airway responses with repeated exposures before and during allergen challenge .