Ongoing research on this topic focuses on exploring the unique roles of the eosinophilic leukocyte in promoting health and restoring homeostasis. We report significant progress on our study focused on eosinophils and their interactions with respiratory virus pathogens in vivo. We have recently documented accelerated clearance of the highly pathogenic mouse pneumovirus pathogen, pneumonia virus of mice (PVM;see AI000943), from the lungs of infected eotaxin-2 / IL-5 double-transgenic (hE2/IL5tg) mice, a unique mouse asthma model that features eosinophils that undergo profound and extensive degranulation. Virus recovery from lung tissue of hE2IL5tg mice is reduced dramatically -- nearly one-thousand fold -- when compared to those from infected wild-type, or minimally eosinophil-enriched single tg mice. Virus clearance and also prolonged survival in response to this lethal infection is directly and completely eosinophil dependent, as we have found that these observations cannot be recapitulated in hE2IL5 double-transgenic mice on a del-dblGATA eosinophil-deficient background. These findings have profound significance not only for our understanding of eosinophils, but for virus infection in the setting of acute and chronic asthma. We also report on a recently published study in which we utilized our highly-cited protocol for the generation of mouse eosinophils from unselected bone marrow progenitors. By using this method, we identified an unusual wild-type mouse strain (Rocky Mountain White, IRW) with aberrant eosinophil hematopoiesis. Interestingly, analysis of IRW bone marrow at baseline was unremarkable, including normal numbers of LSK (Lin-Sca-1+c-kit+) pluripotent stem cells and a normal eosinophil hematopoietic progenitor population. However, in response to conditions in which one would expect eosinophils to be generated, we found relatively diminished expression of the eosinophil-specific interleukin-5 receptor subunit alpha (IL-5Ralpha). Likewise, western blot revealed that IRW bone marrow progenitors over-express the non-signaling soluble IL-5Ralpha decoy protein. As such, while IRW mice can generate airway eosinophilia in response to the classic ovalbumin sensitization and challenge, the response was significantly blunted. For further development of this project, we were fortunate to have Dr. Eva M. Sturm from the Medical University of Graz join our section via fellowship support from the Erwin Schroedinger Foundation (Austria). Eva has utilized our bone marrow progenitor protocol to develop a powerful method for examining receptor-mediated chemotaxis of eosinophils in vivo. This finding has profound implications for preclinical testing of eosinophil inhibitors, specifically those directed against specific receptors and surface antigens. These aforementioned research directions were among those featured in the textbook """"""""Eosinophils in Health and Disease"""""""" (Elsevier Publishers, Inc.), conceived and edited by myself and my collaborator, Dr. James Lee, currently in press (2012).
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