Cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF) are known to trigger the accumulation of eosinophils during inflammatory asthma. However, the mechanism of activation triggered by inflammatory cytokines is not well understood. The Notch 1 receptor on eosinophils has been implicated in vitro in granulocyte-macrophage colony stimulating factor (GM-CSF)-induced eosinophil migration using human eosinophils and in vivo in a mouse model of inflammatory asthma using an anti-Notch antibody (Liu et al. 2015). In order to study the role of the Notch 2 receptor in membrane signaling exclusively in eosinophils, we created a double-mutant knockout mouse with Notch 2 receptor expression ablated only in cells fully committed to the eosinophil lineage. We then characterized the eosinophil-specific Notch 2 knockout mouse in a house dust mite model of inflammatory asthma. Leukocytes were extracted from wild-type and knockout mice from multiple compartments, including bone marrow, blood, and bronchoalveolar lavage fluid. Eosinophils were quantified by cell surface markers during fluorescence-activated cell sorting and by differential cell counts on H&E stained slides. Deletion of Notch 2 on eosinophils resulted in a decreased percentage of eosinophils in bone marrow and systemic blood, but not in bronchoalveolar lavage fluid (BAL). These data suggest that Notch 2 signaling may be important for migration of eosinophils in bone marrow and blood, but that other signaling pathways may be activated in the HDM model of mouse inflammatory asthma. References: Liu, Y.H.; Wang, H.; Xenakis, J.J.; Spencer, L.A. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils. Allergy 2015, 70, 805-812.

Role of Notch 2 receptor signaling during eosinophil activation in a house dust mite model of inflammatory asthma

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.