Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation

Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice ([mrp1.sup.+/+]) and MRP1-deficient mice ([mrp1.sup.-/-]) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in [mrpl.sup.-/-] mice compared with [mrp1.sup+/+] mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed [mrp1.sup.-/-] mice were significantly lower than those from OVA-exposed [mrp1.sup.+/+] mice. Levels of OVA-specific IgE, IL-4, and IL-13 in BALF were also decreased in OVA-exposed [mrp1.sup.-/-] mice. IgE-mediated release of CysLTs from routine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role in the development of allergic airway inflammation through regulation of IgE-mediated CysLT export from mast cells. cysteinyl leukotrienes; mast cell