Effects of interferon-alpha2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis
Autor: | Andreas Chott, Wolfgang Hagen, C Sillaber, E. Spanblöchl, Wolfgang Jurecka, Gerit-Holger Schernthaner, Peter Valent, Wolfgang R. Sperr, H Semper, Klaus Lechner, Klaus Wolff |
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Rok vydání: | 2001 |
Předmět: |
Adult
Male medicine.medical_specialty Tryptase Stem cell factor Internal medicine medicine Humans Mast Cells Systemic mastocytosis Progenitor cell biology Stem Cells Interferon-alpha Cell Differentiation Hematology General Medicine medicine.disease Mast cell Endocrinology medicine.anatomical_structure Immunology biology.protein Myelopoiesis Bone marrow Stem cell Mastocytosis |
Zdroj: | Annals of hematology. 79(12) |
ISSN: | 0939-5555 |
Popis: | Interferon (IFN)-alpha, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-alpha effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex-vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-alpha2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to1,400 ng/ml). PBMNCs were collected before and during IFN-alpha2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-alpha2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-alpha2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha2b. In summary, our data show that IFN-alpha2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment. |
Databáze: | OpenAIRE |
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