DELTA: Do Repeated Pulmonary Exposures to Zinc Induce Sensitization or Adaptation?
Principal Investigator: Ramon Molina, Sc.D.
Almost all exposures to chemicals, particles, or pathogens are chronic. Unfortunately, most animal experiments deal with healthy subjects who are seeing the reagent of interest for the first time. Rarely or never do they produce the same outcomes when the exposures are chronic. We almost always see either adaptation or sensitization. We seek to develop a reproducible animal model to demonstrate either adaptation or sensitization phenomenon and explore the mechanisms responsible. This project leverages a substantial investment already made by multiple supporters. For example, we have shown sensitization in mice intratracheally instilled with Stachybotrys chartarum spores. We found marked increases in lymphocytes and eosinophils, eosinophil-rich granulomas, and goblet cell metaplasia in multiple-instilled mice compared to single dose- or saline-exposed controls. We also saw marked changes in cytokine expression and metabolite profiles in both bronchoalveolar lavage and plasma. Multiple mold exposures also induced significant metabolic changes in lungs but not in plasma. These data suggest possible unique inflammatory mechanisms in chronic exposures to S. chartarum.
We proposed to use zinc, an important component of air pollution particulate matter as well as of a variety of nano-enabled products. We explored differences between single and multiple exposures and then to characterize the metabolic and cellular changes that accompany these alterations. This will be a platform to explore other materials, especially pesticides, to cause sensitization in humans.
The experiments supported by the Hoffman Pilot Grant Program have been completed. We submitted the manuscript for publication.
The results and conclusions from this project have been presented at a seminar in the Molecular Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA.