Anne Solanilla

Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism.

Summary. The adhesion of haematopoietic progenitor cells (HPC) to the bone marrow microenvironment is a process regulated by cytokines. In this study, we have shown that flt3‐ligand (FL), a growth factor that controls early haematopoiesis, regulated the function and expression of the beta‐1 integrins, very late antigen (VLA)‐4 and VLA‐5 on HPC. The modulation of the adhesiveness of HPC by FL was studied by adhesion assays on umbilical vein endothelial cells (HUVEC). Stimulation by FL induced two peaks of increased adhesiveness of HPC. The first peak was at around 30 min and was mechanistically related to an activation of the beta‐1 integrins, mainly VLA‐4 and VLA‐5. The second peak was at around 12 h and was related to increased expression of VLA‐4 and VLA‐5. The control of HPC adhesiveness by FL is a previously unreported property of FL that may be important for the homing and the retention of flt3‐expressing HPC within the bone marrow microenvironment.

Iron particle labeling of haematopoietic progenitor cells: an in vitro study.

We present a method for labeling bone marrow haematopoietic progenitor cells with iron particles. Labeling was assessed by magnetic resonance imaging and electron microscopy. Labeling with iron particles could allow the following by imaging techniques of haematopoietic cells in physiologic and pathologic conditions such as the engraftment of haematopoietic progenitor cells or the migration of myelomonocytic cells in inflammatory diseases.

Differential effect of interferon alpha on chronic myelogenous leukaemia and normal haematopoietic progenitors in a stromal cell co-culture context: role of the flt3 ligand.

Interferon alpha (IFN‐α) is used to treat chronic myelogenous leukaemia (CML) patients. However, its target(s) remain(s) unknown. One possibility is that there is a differing sensitivity of the leukaemic from the normal colony‐forming cell (CFC) compartments to IFN‐α. Co‐cultures of progenitors with stromal cells provide a valuable tool to dissect direct and indirect activities of IFN‐α. In this study, we have used endothelial cells (EC) as a source of stromal cells. In co‐cultures of normal progenitors with EC, IFN‐α increased the generation of clonogenic cells, mainly via an increased production of flt3 ligand (FL) by EC. In contrast, in co‐cultures of CML progenitors with EC, IFN‐α inhibited the generation of clonogenic cells, mainly by direct inhibition on the progenitors, the up‐regulation of FL production by stromal cells being unable to compensate for the direct inhibitory effects of IFN‐α. These data provide evidence for a differential effect of IFN‐α on the growth of CML and normal CFC cells in a stromal context and suggest that an alteration in the response of CML progenitor cells to FL is important in the explanation of this differential effect.

Tissue inhibitor of matrix metalloproteinase‐1 reduces phosphatidylserine exposure on activated and aged platelets

Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy, Division of Haematology, Department of Clinical and Experimental Medicine & BRMA–Amedeo Avogadro University of Eastern Piedmont, Novara, Italy, Division of Haematology and Transplant, Department of Clinical Medicine and Immunological Sciences, University of Siena, Siena, Italy, Laboratory of Experimental Oncology and Lymphoma Unit, Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland, Division of Heamatology, Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy, Haematology Institute, Catholic University ‘‘Sacro Cuore’’, Rome, Italy, Division of Haematology, S.Eugenio Hospital and University of Tor Vergata, Rome, Italy, and ICGEB Outstation-Monterotondo, CNR Campus ‘‘A. Buzzati-Traverso’’, Rome, Italy. E-mail: vgattei@cro.it *RB and MDB contributed equally to this work as first authors.

Blood Platelets and Systemic Sclerosis

Systemic sclerosis (SSc) is characterized by a progressive fibrosis of the perivascular and interstitial connective tissues which can involve the skin, heart, lungs, kidneys, and the gastrointestinal tract. SSc is an uncommon, debilitating condition, associated to a vital risk linked to visceral extensions and has a high case-fatality rate among connectivitis. SSc begins in the vast majority of cases with a Raynaud’s phenomenon, may have a limited or diffuse skin extension, and is often associated to arterial occlusions, digital ulcerations or necrosis. SSc clinical manifestations are heterogeneous and classifications distinguish limited to diffuse disease, depending on the distribution of the skin lesions and organ involvement [1-3]. There is today no curative treatment. Disease susceptibility differs according to sex, age and race, there is a notable familial clustering, and SSc incidence may be rising [4, 5]. The clinical management of the patients still remains a difficult challenge and the pharmacopeia offers limited choices to the clinician to bring relief to patients. Pulmonary, renal and myocardial complications have benefited from the introduction of angiotensin converting enzyme inhibitors, calcium pump inhibitors, prostacyclin analogs and endothelin antagonists. Based on recent pathophysiological insights, a number of novel agents are being developed [6-8].