Submitted May 7, 2008
Accepted January 10, 2009
Mature human eosinophils express functional Notch ligands mediating eosinophil autocrine regulation
Amy L. Radke, Lauren E. Reynolds, Rossana C.N. Melo, Ann M. Dvorak, Peter F. Weller, and Lisa A. Spencer*
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
Department of Biology, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
* Corresponding author; email: lspencer{at}bidmc.harvard.edu.
Eosinophil chemotaxis and survival within tissues are key components in the development of tissue eosinophilia and subsequent effector responses. In this study we demonstrate a novel mechanism of eosinophil auto-regulation affecting migration and survival, mediated through Notch signaling. We show for the first time that human blood eosinophils express Notch receptors and Notch ligands, expressions of which are influenced by the presence of eosinophil-activating GM-CSF. Evidence of Notch receptor activation and subsequent transcription of the Notch-responsive gene HES1 were observed in GM-CSF-stimulated eosinophils, confirming functionality of eosinophil-expressed Notch signaling components. Moreover, by inhibiting Notch signaling with 
-secretase inhibitors or Notch receptor-specific neutralizing antibodies, we demonstrate that autocrine Notch signaling enhances stimulus-mediated actin rearrangement and eosinophil chemokinesis, and impairs eosinophil viability. Taken together, these data suggest autocrine Notch signaling, enhanced in response to tissue- or inflammatory-derived signals, influences eosinophil activity and longevity, which may ultimately contribute to the development of tissue eosinophilia and exacerbation or remediation of eosinophil effector functions.
