Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis.
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.
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Rita
R
Campanelli
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Gabriela
G
Fois
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Paolo
P
Catarsi
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Valentina
V
Poletto
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Laura
L
Villani
Vascular Biology Group, IFOM, FIRC Institute of Molecular Oncology, Milano, Italy.
Benedetta Gaia
BG
Erba
Vascular Biology Group, IFOM, FIRC Institute of Molecular Oncology, Milano, Italy.
Luigi
L
Maddaluno
Unit of Hepatopancreatic Surgery, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Basilio
B
Jemos
Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Silvia
S
Salmoiraghi
Center for Research and Innovation for Myeloproliferative Neoplasms-CRIMM, AOU Careggi, and Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
Paola
P
Guglielmelli
Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Vittorio
V
Abbonante
Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Christian Andrea
CA
Di Buduo
Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.|Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Alessandra
A
Balduini
Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, University of Milano, Milano, Italy.
Alessandra
A
Iurlo
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Giovanni
G
Barosi
Center for the Study of Myelofibrosis, Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Vittorio
V
Rosti
Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy.
Margherita
M
Massa
D000368:Aged; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D055728:Primary Myelofibrosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D042787:Receptor, TIE-2 / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism* / Q000473:pathology; D013156:Splenectomy
D042787:Receptor, TIE-2