title: Interleukin-3 promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation.
abstract: Interleukin-3 (IL-3) released by infiltrating inflammatory cells in different pathologic settings contributes to organ and tumor angiogenesis. Here we demonstrate that IL-3 expands a subset of CD45+ circulating angiogenic cells clonally derived from the hemopoietic progenitors. Moreover, CD45+ cells exposed to IL-3 acquire arterial specification and contribute to the formation of vessels in vivo. Depletion of signal transducer and activator of transcription 5 (STAT5) provides evidence that IL-3-mediated cell expansion and arterial morphogenesis rely on STAT5 activation. In addition, by means of Tie2-transgenic mice, we demonstrate that STAT5 also regulates IL-3-induced expansion and arterial specification of bone marrow-derived CD45+ cells. Thus, our data provide the first evidence that, in inflammatory microenvironments containing IL-3, angiogenic cells derived from hemopoietic precursors can act as adult vasculogenic cells. Moreover, the characterization of the signaling pathway regulating these events provides the rationale for therapeutically targeting STAT5 in these pathologic settings.
authors.affiliation: Department of Internal Medicine, University of Torino, Torino, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Zeoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dentelli
authors.forename: Arturo
authors.initials: A
authors.lastname: Rosso
authors.forename: Gabriele
authors.initials: G
authors.lastname: Togliatto
authors.forename: Antonella
authors.initials: A
authors.lastname: Trombetta
authors.forename: Laura
authors.initials: L
authors.lastname: Damiano
authors.forename: Paola Francia
authors.initials: PF
authors.lastname: di Celle
authors.forename: Luigi
authors.initials: L
authors.lastname: Pegoraro
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
mesh_terms: D000818:Animals; D001158:Arteries / Q000254:growth & development*; D001854:Bone Marrow Cells; D049109:Cell Proliferation; D006413:Hematopoietic System / Q000166:cytology*; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology*; D017493:Leukocyte Common Antigens; D051379:Mice; D018919:Neovascularization, Physiologic; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D013234:Stem Cells
chemical_list: D007377:Interleukin-3; D050799:STAT5 Transcription Factor; D017493:Leukocyte Common Antigens