Abstract

We have demonstrated for the first time that a conditioned medium from a human cell strain can induce morphologically mature mast cells that express Fc epsilon RI and three mast cell-specific proteases from normal bone marrow progenitor cells. In contrast, recombinant human Kit ligand induced the differentiation of mast cells that were tryptase-positive but negative for chymase, carboxypeptidase, and Fc epsilon RI. This data indicates that factors other than Kit ligand are critical for inducing the differentiation and maturation of mast cells in the human. The HBM-M cell was originally derived from a patient with mastocytosis. As mastocytosis is thought to represent a reactive hyperplasia rather than a mast cell malignancy, the factor secreted by the HBM-M cell strain could well be responsible for the mast cell hyperplasia seen in some patients with mastocytosis.

Highlights

  • From the :j:University of New South Wales, School of Medicine, Kensington 2033, the §Departments of Immunology, Allergy and Infectious Disease, and ]]Oncology, St

  • While neither IL-3 nor IL-4 by themselves induces human hematopoietic progenitor cells to differentiate into mast cells [19, 20], morphologically immature populations of human mast cells are obtained when hematopoietic progenitor cells from nonnal bone marrow, peripheral blood, fetal liver, or umbilical cord blood are cultured in the presence of recombinant human KL [21,22,23]

  • In the present study we show that conditioned media from this cell strain will induce bone marrow progenitor cells from normal subjects to preferentially differentiate into mast cells that express tryptase, chymase, carboxypeptidase, and FceRI

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Summary

THE JOURNAL OF BIOLOGICAL CHEMISTRY

VoL 270, No 5, Issue of February 3, pp. 2258-2263, 1995 Printed in U.S.A. Conditioned Media from a Cell Strain Derived from a Patient with Mastocytosis Induces Preferential Development of Cells That Possess High Affinity lgE Receptors and the Granule Protease Phenotype of Mature Cutaneous Mast Cells*. Recombinant human Kit ligand induced the differentiation of mast cells that were tryptase-positive but negative for chymase, carboxypeptidase, and FceRI. Furitsu and co-workers [42] reported that mature, chymase+/tryptase+ mast cells were obtained when human cord blood mononuclear cells were cocultured with mouse 3T3 fibroblasts In subsequent studies, these investigators found that fibroblast conditioned media containing soluble KL could induce stem cells from human cord blood to differentiate into a population of immature mast cells that expresses tryptase but not chymase [21, 36]. In the present study we show that conditioned media from this cell strain will induce bone marrow progenitor cells from normal subjects to preferentially differentiate into mast cells that express tryptase, chymase, carboxypeptidase, and FceRI

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