Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells.

Abstract

SummaryThe effect of nerve growth factor (NGF) on proliferation/differentiation of mast cells was investigated in vitro. Although NGF alone neither supported colony formation of bone marrow-derived cultured mast cells (BMCMC) nor induced development of mast cell colonies from nonadherent bone marrow cells (NBMC), addition of NGF to the suboptimal dose of interleukin 3 (IL3) significantly increased the numbers of mast cell colonies produced by BMCMC or NBMC in methylcellulose. When stimulated by IL3 alone, cells in mast cell colonies were not stained by berberine sulfate, a fluorescent dye. In contrast, mast cells developing in methylcellulose cultures obtaining both 11,3 and NGF were stained by berberine sulfate. The fluorescence was abolished by the treatment of heparinase but not of chondroitinase ABC, suggesting that mast cells stimulated by 11,,3 and NGF produced and stored heparin proteoglycan . The histamine content of BMCMC maintained by IL-3 was also increased by addition of NGF. Since BMCMC showed mucosal mast cell-like phenotype, NGF appeared to induce the phenotypic change to connective tissue-type mast cells (CTMC) . In the culture containing BMCMC, 3T3 fibroblasts, and IL-3, the phenotypic change of BMCMC to CTMC was observed as well . Since NGF was detected in this coculture and since addition of anti-NGF monoclonal antibody suppressed the phenotypic change, NGF produced by fibroblasts appeared to induce the phenotypic change. Neither BMCMC alone nor IL3 alone increased the concentration of NGF. Therefore, there is a possibility that BMCMC stimulated by IL3 may induce the production and/or release of NGF by fibroblasts .

Nerve Growth Factor Activates Mast Cells Through the Collaborative Interaction with Lysophosphatidylserine Expressed on the Membrane Surface of Activated Platelets

“…In addition to neurotrophic activity, increasing evidences give rise to possible multifunctional properties of NGF on immunocompetent cells including lymphocytes, monocytes/macrophages, and mast cells through functional NGF receptors (4 -11). In prior studies, we have demonstrated that NGF promotes not only granulocyte differentiation from human PBMC and murine bone marrow cells (12,13), but also differentiation of connective tissue-type mast cells from murine bone marrow cells and bone marrow-derived culture mast cells (14). NGF is capable of supporting survival of neutrophils (15), eosinophils (16), and mast cells (9) by preventing apoptosis, and enhancing functional properties of neutrophils, eosinophils, macrophages, and mast cells: phagocytosis, superoxide production, matrix metalloproteinase-9 production, and chemotaxis (11, 12, 16 -20).…”

Stem Cell Factor Has a Suppressive Activity to IgE-Mediated Chemotaxis of Mast Cells

“…The marked effect of SCF was noted even after preincubation for 1 h and most BMCMC preincubated for 48 h remained in the upper compartment. NGF, which is produced by fibroblasts as SCF, promotes differentiation and chemotaxis of mast cells (9,49). Therefore, we examined its effect on the IgEmediated chemotaxis of BMCMC.…”

Differential roles of GATA‐1 and GATA‐2 in growth and differentiation of mast cells

“…Mature CTMCs contain more histamine and heparin, which is specifically recognized with berberine sulphate, than those in mucosal type mast cells. Both of these types of mature mast cells can be mutually interconverted by simply altering the culture conditions in vitro or the environment in vivo (Matsuda et al 1991). Thus, these two classes of mature mast cells have clearly defined and unique characteristics; the molecular determinants which specify their differentiation, in contrast, are not understood.…”