Regulation of Mast Cell Development by Inflammatory Factors

Abstract

Mast cells are potent effectors playing a key role in IgE-associated hypersensitivity reactions, allergic disorders, inflammation and protective immune responses. Mast cell development in vivo occurs mainly in non-hematopoietic microenvironments and increased mast cell numbers can be seen in various inflammatory diseases and pathologic conditions. SCF (also known as kit ligand or KitL) and c-kit signaling are essential for both human and murine mast cell development, while IL-3 is required for murine mast cell hyperplasia that occurs in response to various stimuli. Besides SCF and IL-3, the cytokines IL-4, IL-9, IL-10 and IL-13 are also called mast cell growth factors due to their actions synergistically promoting mast cell proliferation and differentiation in the presence of SCF or IL-3. These cytokines alone however are unable to support neither the proliferation nor survival of mast cells. Most research has focused on examining the direct effects of the above cytokines on mast cells or their precursors. However, it is difficult to explain the process of mast cell development only in terms of the above mast cell growth factors. A series of experiments in our laboratory and by others has revealed that inflammatory mediators and cytokines, as triggers or regulators, are also crucial for mast cell development. This review summarizes recent progress in our understanding of how various inflammatory factors regulate mast cell development, with particular focus on the effects of prostaglandin E (PGE), TNF-alpha, IL-6, IFN-gamma and an unknown apoptosis-inducing factor produced by IL-4-stimulated macrophages.

Interleukin‐17–positive mast cells contribute to synovial inflammation in spondylarthritis

“…Results of ELISA revealed similar levels of SCF in SpA synovial fluid (median 569 pg/ml, IQR 539-681 pg/ml) and RA synovial fluid (median 522 pg/ml, IQR 425-629 pg/ml). The synovial fluid levels of another important factor for mast cell survival, IL-3 (27), were undetectable in the majority of samples, and were not different between SpA and RA synovial fluid (results not shown).…”

SHIP1 Is a Repressor of Mast Cell Hyperplasia, Cytokine Production, and Allergic Inflammation In Vivo

“…TNF is required for mast cell development and stimulates mast cell colony formation in vitro (24,25). In addition, IL-6 promotes mast cell development from mixed cultures, likely via a secondary mediator such as PGE (24). We suspect that the systemic mast cell hyperplasia observed in Ship1 Ϫ/Ϫ mice is also due to the hypersensitivity of Ship1 Ϫ/Ϫ mast cells to stimulation with SCF or IgE (without crosslinking Ag) (6,11).…”

“…TNF is required for mast cell development and stimulates mast cell colony formation in vitro (24,25). In addition, IL-6 promotes mast cell development from mixed cultures, likely via a secondary mediator such as PGE (24).…”

Contribution of Fibroblast and Mast Cell (Afferent) and Tumor (Efferent) IL-6 Effects within the Tumor Microenvironment

“…Since active, degranulating mast cells secrete IL-6 (reviewed in [31,36,37]) and IL-6 is important for mast cell development [40], and given the potential role of mast cells in the tumor stroma, we went back to our xenograft models to examine whether mast cells were present.…”