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EFFECT OF PARTICULATE MATTER (PM) COLLECTED IN TWO EUROPEAN CITIES ON ALLERGIC SENSITIZATION AND ALLERGIC RESPONSES IN MICE
Impact/Purpose:
This work will support epidemiological observations of differences in allergenicity of PM from two European cities with differing levels of air pollution by providing evidence in an animal model for plausible mechanisms by which PM2.5 may affect allergic asthma.
Description:
Children (5-14 years old) living in the industrial city of Hettstedt (H) in eastern Germany were reported to have a higher incidence of sensitization to common aeroallergens compared to another cohort living in the nearby city of Zerbst (Z) which has less industrial pollution (Heinrich, Environ Health Perspect 107:53, 1999). The objective of this study was to examine effects of extracts of fine particulate matter (PM 2.5) filters collected from these two cities (January-June 1999) or control (C) filters on responses to ovalbumin (OVA) antigen in mice. To examine effects on the sensitization phase, BALB/c mice were exposed by intratracheal (i.t.) instillation to 50 ug PM in 50 ul saline 2 hr prior to i.t. sensitization with OVA in 50 ul saline. This i.t. exposure/sensitization was repeated 2 d later, and mice were challenged with i.t. OVA 12 d later. To examine effects on the challenge phase, BALB/cJ mice were sensitized with OVA/adjuvant i.p., exposed 14 d later i.t. to 100 mg PM, and then challenged i.t. with OVA 2 hr later. H and Z given prior to challenge, but not prior to sensitization, increased immediate bronchoconstriction (enhanced pause, PenH) to OVA challenge (190% (P < 0.05) and 120%, respectively, vs. prechallenge baseline). Two days after challenge, responsiveness to methacholine aerosol was significantly greater in mice exposed at challenge to H, but not Z, vs. C. There were no differences in bronchoalveolar lavage (BAL) cell profiles in mice exposed prior to sensitization. Only Hettstedt particles administered at challenge significantly increased BAL eosinophils, neutrophils, and lymphocytes (each ~3-fold). Both Hettstedt and Zerbst particles administered at challenge increased BAL lung injury parameters and BAL TNF-a and IFN-g, but Th2 cytokines were not significantly increased. These results indicate that exposure to PM prior to challenge augments pathophysiologic responses associated with allergic asthma.