594
The Murine Pulmonary Proteomic Profile Associated with Allergic Aspergillus Fumigatus Exposure
Sunday, March 6, 2016: 2:45 PM
Room 502A (Convention Center)
Ajay P. Nayak, PhD, , , , , , ,
Rationale: Quantitative proteomics is an approach that complements existing methodologies available to examine disease state and enable biomarker discovery. We aimed to examine the alterations in the lung proteome following repeated inhalation of Aspergillus fumigatusconidia in a murine model of fungal allergy.

Methods: Naïve B6C3F1/n mice inhaled viable A. fumigatus conidia (105) or HEPA-filtered air (control) twice a week for 13 weeks. Proteins from lung homogenates were separated by SDS-PAGE, and analyzed by nano LC/MS/MS with a Waters NanoAcquity system by MS Bioworks. Acquired peptide-ions were searched against the Mus musculusdatabase. The resultant spectral count (SpC) dataset was assessed to evaluate differences in abundance between viable and air control group.

Results: In mice exposed to viable conidia, 143 proteins were identified in increased abundance. Chitinase like-proteins 3 and 4, were identified as most abundant proteins (10-50 fold higher SpC vs control) associated with allergic inflammation. Antimicrobial proteins S100-A9 and surfactant protein D were also significantly more abundant in lungs of these mice (3-5 fold higher Spc vs control). Repeated microbial insult resulted in hypoxic microenvironment as evident by increased abundance of hypoxia regulated protein. Vigilin, a novel marker with uncharacterized role was also significantly abundant (3 fold higher Spc vs control) in exposed mice.

Conclusions: This study demonstrates shifts in pulmonary proteomic profile following chronic fungal exposure. The study also highlights the utility of SpC metrics in determining the abundance of specific protein markers and underlines a significant role for identified proteins in disease progression in the described model.