A Phenotypic Screening Approach in Cord Blood–Derived Mast Cells to Identify Anti-Inflammatory Compounds

摘要: Mast cells are unique hematopoietic that richly distributed in the skin and mucosal surfaces of respiratory gastrointestinal tract. They play a key role allergic inflammation by releasing cocktail granular constituents, including histamine, serine proteases, various eicosanoids cytokines. As such, number drugs target either inhibition mast cell degranulation or products degranulation. To identify potential novel mechanisms biology, assays were developed to inhibitors activation phenotypic screen. Due challenges associated with obtaining primary cells, cord blood–derived mononuclear reproducibly differentiated monitor tryptase release prostaglandin D 2 generation. The assay was particularly sensitive, requiring only 500 per data point, which permitted set approximately 12,000 compounds be screened robustly cost-effectively. Active tested for concomitant D2 This study demonstrates robustness effectiveness this approach identification targeting cell–driven inflammation, enable innovative drug discovery efforts prosecuted.