title: Defective eosinophil hematopoiesis ex vivo in inbred Rocky Mountain White (IRW) mice.
abstract: We examine the proliferation and differentiation of bone marrow (BM) progenitors from inbred Rocky Mountain White (IRW) mice, a strain used primarily for retrovirus infection studies. In contrast to findings with BALB/c and C57BL/6 strains, IRW BM cells cannot proliferate or generate pure eosinophil cultures ex vivo in response to a defined cytokine regimen. Analysis of IRW BM at baseline was unremarkable, including 0.08 ± 0.03% Lin(-)Sca-1(+)c-kit(+) (LSK) hematopoietic stem cells and 5.2 ± 0.3% eosinophils; the percentage of eosinophil progenitors (EoPs; Lin(-)Sca-1(-)c-kit(+)CD34(+)IL-5Rα(+)) was similar in all three mouse strains. Transcripts encoding GM-CSFRα and the IL-3/IL-5/GM-CSF common β chain were detected at equivalent levels in IRW and BALB/c BM, whereas expression of transcripts encoding IL-5Rα, IL-3Rα, and GATA-2 was diminished in IRW BM compared with BALB/c. Expression of membrane-bound IL-5Rα and intracellular STAT5 proteins was also diminished in IRW BM cells. Diminished expression of transcripts encoding IL-5Rα and GATA-2 and immunoreactive STAT5 in IRW BM persisted after 4 days in culture, along with diminished expression of GATA-1. Western blot revealed that cells from IRW BM overexpress nonsignaling soluble IL-5Rα protein. Interestingly, OVA sensitization and challenge resulted in BM and airway eosinophilia in IRW mice; however, the responses were significantly blunted. These results suggest that IRW mice have diminished capacity to generate eosinophils in culture and in vivo, likely as a result of diminished signaling via IL-5Rα.
authors: Eosinophil Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy andInfectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. kdyer@niaid.nih.gov
authors: Kimberly D
authors: KD
authors: Dyer
authors: Katia E
authors: KE
authors: Garcia-Crespo
authors: Caroline M
authors: CM
authors: Percopo
authors: Aaron B
authors: AB
authors: Bowen
authors: Tomonobu
authors: T
authors: Ito
authors: Karin E
authors: KE
authors: Peterson
authors: Alasdair M
authors: AM
authors: Gilfillan
authors: Helene F
authors: HF
authors: Rosenberg
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D038042:Myelopoiesis / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
chemical_list: D010047:Ovalbumin