Tissue mast cells and the closely related blood basophils are distinguished by their special mediators and their high-affinity IgE membrane receptors. These properties have made the cells be viewed traditionally as effector cells of immediate-type hypersensitivity reactions. More recently, mast cells have been shown to develop from the myeloid series of the bone marrow under the influence of interleukins 3, 4, 6, 9, 10 and 11. Mast cell and basophil lines of murine and human origin have also been shown to express and release interleukins 1, 3, 4, 5, 6, 8, tumor necrosis factor-α, granulocyte-macrophage colony-stimulizing factor and interferon-γ. Certain cytokines are also able to induce mediator release from mast cells. Furthermore, mast cells have in the past been shown to be modestly phagocytic and to express major histocompatibility complex class II membrane markers after appropriate stimulation. These findings show that mast cells are intricately associated with immune reactions and suggest that they may not only sustain and modulate but possibly also initiate immune responses.
The basic understanding of mast cell ontogeny and function has been fundamentally changed in recent years with observations that the cells produce and respond to a broad range of cytokines. These rapidly accruing data and their potential significance were discussed at the recent symposium "Mast Cells in the Cytokine Network", and the overview lectures of most speakers are summarized in this special journal issue. In the present introductory manuscript, the organizers of the meeting discuss data fundamental to an understanding of the topic and highlight aspects of special interest. They consider mast cells to be defined most reliably by their unique ultrastructure since the cells are highly heterogeneous in dependence of the species studied, their tissue location, their stage of development and probably also in relation to cytokines. Most other characteristics of mast cells are shared with diverse other cell types. Murine mast cell development is induced by several cytokines. These factors are mostly ineffective in human cells except for stem cell factor which causes mast cell development from CD34+/c-kit+ progenitors. There is however recent evidence that fibroblasts and keratinocytes produce additional growth factors for human mast cells. Regarding cytokine secretion, most molecules known so far are produced by both murine and human mast cells. The cells furthermore bear receptors for several cytokines, enabling them to respond in an autocrine and paracrine fashion. Mast cells may thus function within a complex cytokine network, affecting physiological as well as immunological and inflammatory processes.
Mast cell differentiation markers were studied by culturing monocytic (U937, THP1) a promyelotic (HL60) and a human mast cell line (HMC1) and peripheral human blood monocytes with fibroblast supernatants and feeder layers. Mast cell differentiation occurred on the basis of metachromasia, chloroacetate esterase, expression of mast cell-specific antigens (APAAP) and production of tryptase in all cell types, but to varying degrees and not at all with a FcεRI marker in monocytic lines. Direct cellular contact is thus not necessary for induction of mast cell differentiation by fibroblasts.
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