Tie2 expressing monocytes in the spleen of patients with primary myelofibrosis

Rita Campanelli, Gabriela Fois, Paolo Catarsi, Valentina Poletto, Laura Villani, Benedetta Gaia Erba, Luigi Maddaluno, Basilio Jemos, Silvia Salmoiraghi, Paola Guglielmelli, Vittorio Abbonante, Christian Andrea Di Buduo, A. Balduini, Alessandra Iurlo, Giovanni Barosi, Vittorio Rosti, Margherita Massa, Alessandro M. Vannucchi, M. Balliu, Niccolò BartalucciCostanza Bogani, Alberto Bosi, L. Calabresi, G. Corbizzi Fattori, Tiziana Fanelli, Rajmonda Fjerza, F. Gesullo, Paola Guglielmelli, C. Mannarelli, L. Merli, Annalisa Pacilli, A. Pancrazzi, Chiara Paoli, Lisa Pieri, G. Rotunno, Emanuela Sant'Antonio, G. Barosi, Vittorio Abbonante, A. Balduini, Elisa Bonetti, R. Campanelli, P. Catarsi, Christian A. Di Buduo, G. Fois, M. Massa, V. Poletto, V. Rosti, L. Villani, Mario Cazzola, Ilaria Ambaglio, Paolo Bernasconi, C. I. Casetti, Silvia Catricala, Chiara Elena, Elena Fugazza, Anna Gallì, Luca Malcovati, Chiara Milanesi, Cristiana Pascutto, Daniela Pietra, Francesco Ripamonti, Marianna Rossi, Elisa Rumi, Elisabetta Dejana, Ferruccio Breviario, Monica Corada, M. Malinverno, Alessandro Rambaldi, G. Chioda, Maria L. Ferrari, Guido Finazzi, Mariachiara Finazzi, Clara Belotti, C. Boroni, S. Salmoiraghi, A. Amaru, Josée Golay, S. Bortoluzzi, Andrea Bisognin, Alessandro Coppe, C. Saccoman, Rossella Manfredini, Lucia Artuso, Isabella Bernardis, Elisa Bianchi, Monica Montanari, Valentina Pennucci, Zelia Prudente, Sebastiano Rontauroli, C. Rossi, Samantha Ruberti, Simona Salati, Enrico Tagliafico, Elena Tenedini, R. Zini

Research output: Contribution to journalArticle

Abstract

Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph-) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62-CCR2- (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ.

Original languageEnglish
Article numbere0156990
JournalPLoS One
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Campanelli, R., Fois, G., Catarsi, P., Poletto, V., Villani, L., Erba, B. G., Maddaluno, L., Jemos, B., Salmoiraghi, S., Guglielmelli, P., Abbonante, V., Di Buduo, C. A., Balduini, A., Iurlo, A., Barosi, G., Rosti, V., Massa, M., Vannucchi, A. M., Balliu, M., ... Zini, R. (2016). Tie2 expressing monocytes in the spleen of patients with primary myelofibrosis. PLoS One, 11(6), [e0156990]. https://doi.org/10.1371/journal.pone.0156990