Mast cell deficient mice display a pulmonary Th2 polarization with an increase in alternatively activated alveolar macrophages (151.17)

Abstract

Abstract Macrophages are innate immune cells capable of coordination with the adaptive immune system during an immune response. The classical activation of macrophages is induced by IFN-γ, while the alternative activation of macrophages is triggered by IL-4 and IL-13. Mast cells are well recognized for their role in allergic inflammation, asthma and innate immunity. Due to a membrane tyrosine kinase mutation in c-Kit, B6.Cg-KitW-sh mice are unable to respond to stem cell factor and therefore do not develop mast cells. Thus, B6.Cg-KitW-sh mice do not develop IgE -dependent passive cutaneous anaphylaxis in the ear and joint as well as passive anaphylaxis. In the current study, we show that B6.Cg-KitW-sh mice display a Th2 phenotype with elevated levels of IL-4, IL-5 and IL-13 in serum and decreased IFN-γ levels in lung BAL fluid. This data led us to investigate whether alveolar macrophage phenotype is altered due to mast cell deficiency. We found an increase in the expression of genes associated with alternative activation of alveolar macrophages that included arginase-1 (Arg1), chitinases (Chi313), and FIZZ1 (Retnla) in BAL cells, when compared to background control mice (C57BL/6). In addition, these alternative activated macrophages display a > 25 fold change in class B scavenger receptor (Scarb2) expression. These data begin to suggest that mast cells may be important in regulation of alveolar macrophage phenotype.