Unique populations of lung mast cells are required for antigen-mediated bronchoconstriction (86.11)

Abstract

Abstract Several studies implicate mast cells as important effector cells of anaphylaxis. Much of our understanding of the functions of mast cells emanates from the study of mice lacking theses cells, particularly mice carrying mutations in c-Kit. Definitive evidence for the role of mast cells in these mice requires the normalization of altered immune responses by reconstitution with cultured mast cells (BMMC). While many niches can be restored with BMMC, this has not been demonstrated for mast cells present in the airways of the lung, cells poised to mediate bronchoconstriction during allergic responses. To determine if mast cell reconstitution is an appropriate model for the study of bronchoconstriction associated with allergic responses, KitWsh/Wsh mice were engrafted with either whole bone marrow (WBM) or BMMC and responses to IgE-mediated anaphylaxis determined. Engraftment of KitWsh/Wsh mice with WBM or BMMC results in reconstitution of the central airways with mast cells. While the treatment of both groups results similar systemic changes in a model of passive anaphylaxis, bronchoconstriction was observed only in animals which received WBM. While BMMC can populate the lung, they cannot restore IgE/Ag-mediated bronchoconstriction to mast cell-deficient animals. This suggests the mast cell population mediating this function may be unique, and to fill this niche in the lung cells must undergo a specific developmental program that is no longer available to cultured mast cells.