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  • Interferon-α  (1)
  • toxic histamine release  (1)
  • 1
    ISSN: 1432-0584
    Keywords: Keywords Mastocytosis ; Progenitor cells ; Interferon-α ; Tryptase ; Histamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Interferon (IFN)-α, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-α 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-α2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to 〉1400 ng/ml). PBMNCs were collected before and during IFN-α2b 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-α2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-α2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-α2b 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-α2b. In summary, our data show that IFN-α2b 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-α treatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0021-9304
    Keywords: basophils ; mast cells ; metal ions ; toxic histamine release ; apoptosis ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: Recent data suggest that distinct metal ions can be released from dental alloys or other biomaterials, and may cause toxic effects on various cells. In this study, the effects of 14 metal ions on histamine release from human blood basophils (n = 4), isolated tissue mast cells (lung n = 8, uterus n = 2, skin n = 1, gingiva n = 1), the basophil cell line KU-812, and the mast cell line HMC-1 were analyzed. Of the 14 metal ions, Ag+ (0.33 mM) and Hg2+ (0.33 mM) were found to induce release of histamine in blood basophils, KU-812, mast cells, and HMC-1. The effects of Ag+ and Hg2+ were dose dependent and were observed within 60 min of incubation. In primary mast cells and basophils, Au3+ (0.33 mM) also induced histamine release, whereas no effects of Au3+ on HMC-1 or KU-812 cells were seen. The other metal ions showed no effects on primary or immortal cells within 60 min. However, Pt4+ (0.33 mM) induced histamine liberation in HMC-1 and lung mast cells after 12 h. The Ag+- and Hg2+-induced rapid release of histamine from HMC-1 was associated with ultrastructural signs of necrosis, but not apoptosis. In contrast, prolonged exposure to Pt4+ (0.33 mM, 14 h) induced apoptotic cell death in HMC-1 cells, as assessed by electron microscopy and DNA analysis. Together, certain metal ions induce distinct cytopathogenic effects in mast cells and basophils. Whereas Ag+, Hg2+, and Au3+ cause direct toxicity, Pt4+ causes cell death through induction of apoptosis. Whether such effects contribute to local adverse reactions to metal-containing biomaterials in vivo remains to be determined. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 560-567, 1998.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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