P04 - Toxicant sensing by TRP channels in lung macrophages
Members of the superfamily of transient receptor potential (TRP) channels serve as direct or indirect cellular sensors after toxic lung damage from the outer airway or the inner vascular site. On a cellular level, alveolar macrophages (AMΦ) are the first-line defenders of the alveoli and airways, while lung interstitial macrophages (IMΦ) act as gatekeepers of the vasculature and the pulmonary interstitium.
In our project 04, we will analyze the function of TRPV2 in AMΦ and TRPM2 in IMΦ in toxicant sensing using TRP-deficient mouse models and cellular as well as molecular approaches:
• Challenging of mouse models and isolated MΦ by nanoparticles, radioactivity and alkylating agents
• Up- and downregulation of cellular proteins by recombinant lentiviral vectors expressing siRNAs
• Ca2+ imaging analysis
• Phagocytosis and viability assays
• Quantification of cytokine production by ELISAs
Recently identified specific modulators of these channels and their potential as new therapeutic options for preventing toxic lung damage will also be evaluated.