Submitted December 12, 2007
Accepted March 24, 2008
Interleukin-3 (IL-3) promotes expansion of hemopoietic-derived CD45+ angiogenic cells and their arterial commitment via STAT5 activation
Annarita Zeoli, Patrizia Dentelli, Arturo Rosso, Gabriele Togliatto, Antonella Trombetta, Laura Damiano, Paola Francia di Celle, Luigi Pegoraro, Fiorella Altruda, and Maria Felice Brizzi*
Department of Internal Medicine, University of Torino, Torino
Department of Genetics, Biology and Biochemistry, Molecular Biotechnology Center, University of Torino, Torino
Center for Experimental Research and Clinical Studies (CERMS), Azienda Ospedaliera S. Giovanni Battista, Torino
* Corresponding author; email: mariafelice.brizzi{at}unito.it.
Interleukin-3 (IL-3) released by infiltrating inflammatory cells in different pathological settings contributes to organ and tumor angiogenesis. Herein 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 directly contribute to the formation of vessels in vivo. Depletion of STAT5 provides evidences 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 microenvironment containing IL-3, angiogenic cells derived from hemopoietic precursors can act as adult vasculogenic cells. Moreover, the characterization of the signalling pathway regulating these events provides the rational for therapeutically targeting STAT5 in these pathological settings.
