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Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease
Citation:
ZHU, W., A. D. LEDBETTER, P. A. EVANSKY, AND M. I. GILMOUR. Acrolein Exposure Blocks Down-Regulation of Cytokines and IgE Antibody in a Mucosal Tolerance Model but does not Alter Phenotypic Markers of Allergic Lung Disease. Presented at Annual American Thoracic Society, San Diego, CA, May 15 - 20, 2009.
Impact/Purpose:
The purpose of this study is to test the effect of Acrolein exposure on development of immune tolerance and initiation allergic airway disease by using murine model.
Description:
Acrolein (ACR) is a highly reactive upper airway toxicant that humans are exposed in a variety of environmental situations. Here we examined the effect of ACR exposure on development of immune tolerance in mice. To induce tolerance, female BALB/C mice were intranasally inoculated with ovalbumin (OVA) or non-tolerizing saline for 3 consecutive days. Immediately prior to each treatment, animals were exposed by inhalation to either air or 3 ppm ACR for 3 hours. To induce allergic lung disease, two weeks later all mice were injected i.p. with OVA/Al(OH)3 and after a further two weeks, challenged intranasally with OVA for three days. Two days after the last challenge immune responses, pulmonary function and inflammatory parameters were measured and compared between tolerized and non-tolerized mice. Following OVA immunization and challenge the non-tolerized (saline) controls had significantly higher protein, LDH and eosinophils in lung lavage and higher responsiveness to methacholine than the actively tolerized mice and these responses were not affected by prior exposure to ACR. In contrast, previous exposure to ACR reduced serum OVA-specific IgG1 in non-tolerized mice, and enhanced OVA-specific IgE in both tolerized and non-tolerized animals. In addition, the diminution of antibody levels by the tolerizing process was blocked by ACR exposure. Analysis of immune and pro-inflammatory cytokines in draining lymph nodes showed that these mediators were down-regulated in tolerized versus non-tolerized mice and that prior exposure to ACR blocked this effect. We conclude that inhalation of ACR can reverse tolerizing signals in draining lymph nodes and while this translates into replenished IgE production, it does not result in differences in inflammatory and pulmonary function changes following antigen sensitization and challenge. (This abstract does not reflect EPA policy).