RESUMO
Neuropilins and semaphorins are known as modulators of axon guidance, angiogenesis, and organogenesis in the developing nervous system, but have been recently evidenced as also playing a role in the immune system. Here we describe the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human thymus, in both lymphoid and non-lymphoid compartments. SEMA3F have a repulsive effect on thymocyte migration and inhibited CXCL12- and sphingosine-1-phosphate (S1P)-induced thymocyte migration by inhibiting cytoskeleton reorganization prior to stimuli. Moreover, NRP2 and SEMA3F are expressed in human T-cell acute lymphoblastic leukemia/lymphoma primary cells. In these tumor cells, SEMA3F also blocks their migration induced by CXCL12 and S1P. Our data show that SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions.
Assuntos
Movimento Celular/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Neuropilina-2/genética , Células Precursoras de Linfócitos T/metabolismo , Anticorpos Bloqueadores/imunologia , Anticorpos Bloqueadores/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/farmacologia , Criança , Pré-Escolar , Expressão Gênica , Humanos , Lactente , Recém-Nascido , Lisofosfolipídeos/farmacologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/farmacologia , Microscopia Confocal , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Neuropilina-2/imunologia , Neuropilina-2/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Timócitos/metabolismo , Timo/citologia , Timo/metabolismoRESUMO
INTRODUCTION: Mobilization techniques for autologous peripheral blood stem cell (PBSC) collection include chemotherapy followed by hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF). Biosimilar versions of G-CSF are now available in Europe. METHODS: In this study, 40 patients with a hematological malignancy scheduled to receive biosimilar G-CSF (Zarzio(®) Sandoz Biopharmaceuticals, Paris, France) following first-cycle chemotherapy for treatment and autologous PBSC mobilization were prospectively included at a single center. These patients were compared with a historical control group who had been treated with G-CSF (Neupogen(®) Paris, France) at the same center according to the same clinical protocol. PBSC harvesting was considered successful if at least 3×10(6) CD34+ cells/kg were collected. If three consecutive CD34+ tests were below 10/µL then PBSC harvesting was not performed. RESULTS: Patient characteristics were similar in both groups with no significant differences in age, diagnosis, previous chemotherapy, or chemotherapy mobilization regimen. No significant differences were observed between groups in median CD34+ cells mobilized and collected, or the number of G-CSF injections and leukaphereses required to obtain the minimal CD34+ cell count. Proportion of failures was also similar in both groups. CONCLUSION: Zarziois(®) comparable to Neupogen(®) for PBSC mobilization and collection after chemotherapy and so may provide a more cost-effective strategy.