International Immunology, Vol. 14, No. 4, pp. 381-387,
April 2002
© 2002 Japanese Society for Immunology
Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice
1 Department of Genetics, Cell and Immunobiology, Faculty of Medicine, Semmelweis University, 1089 Budapest, Hungary 2 Department of Immunology, Eotvos Lorand University, 1089 Budapest, Hungary 3 Molecular Immunology Research Group, Hungarian Academy of Sciences, 1089 Budapest, Hungary 4 Mount Sinai Hospital Research Institute, Toronto M5G 1X5, Canada
Correspondence to: A. Falus, Department of Genetics, Cell and Immunobiology, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary; E-mail: faland{at}dgci.sote.hu
Transmitting editor: E. Möller
Mast cells are differentiated in vitro from bone marrow precursors. In this study the development of bone marrow-derived mast cells was examined from histidine decarboxylase deficient (HDC–/–) and wild-type mice in the presence of IL-3. The number of non-adherent, tryptase- and c-kit-positive mast cells in bone marrow-derived cultures of HDC–/– mice was decreased compared to that of wild-type (HDC+/+) animals, but within the tryptase- and c-kit-positive cells there was no difference in the expression intensity of both markers between the two groups. Furthermore, less serine proteases mMCP5, mMCP6 and Fc
RI
mRNA were detected in bone marrow-derived cell cultures originating from HDC–/– mice. Antigen-provoked degranulation through high-affinity FcI receptor was also lower in HDC–/– mice. The colony assays in semisolid medium yielded a significantly lower ratio of mixed colonies and higher proportion of macrophage colonies from HDC–/– mice-derived bone marrow compared to the wild-type. In the course of the differentiation of HDC–/– -derived mast cells exogenously added histamine is unable to substitute the endogenously missing histamine. Concordantly, -fluoromethyl-histamine, the specific inhibitor of HDC, revealed only a marginal inhibition on the differentiation of tryptase-positive mast cells from wild-type mice. These findings suggest that the effect of histamine on the IL-3-dependent development of bone marrow-derived mast cell differentiation during the early period is crucial and irreplaceable.
Keywords: bone marrow, differentiation, c-kit, gene targeting, histamine, IL-3, mast cell, tryptase
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