The regulation of mast cell growth and differentiation depends upon the sequential availability of specific growth factors and the expression of their corresponding receptors. Among the various cytokines that promote mast cell growth, the most important is now believed to be stem cell factor (SCF). SCF is produced in peripheral tissues by stromal cells and supports mast cell survival at these sites. We have now found that the decrease in mast cells observed in tissues that follows topical steroid administration as a treatment for allergic inflammation, is due to a direct effect of the steroid on SCF production required for the survival of local mast cells. Similarly, we have identified a mast cell line that lacks the receptor for SCF, c-kit. These mast cells were used to confirm SCF effects on mast cells including proliferation, adhesion, and enhanced releasibility. As an extension that mast cells undergo apoptosis following SCF deprivation, we explored whether mast cells undergo apoptosis in response to activation through Fas antigen (CD95, APO-1), thus providing an additional pathway that could contribute to the regulation of mast cell numbers. The murine cell line, C57, was found to rapidly undergo apoptosis following aggregation of Fas antigen. Primary cultures of IL-3 or SCF-dependent murine bone marrow derived mast cells were relatively resistant to anti-Fas antibody alone. These data support the conclusion that activation of the Fas pathway provides an additional mechanism by which mast cell numbers may be regulated. The effector function of mast cells in both IgE-dependent and in immune complex-induced inflammation is in part determined by the interaction of mast cells with connective tissue matrix components. This influences mast cell chemotaxis, tissue location, and biologic reponsiveness. We have now reported several observations that contribute to the understanding of the role of mast cells in inflammatory diseases. First, we have found that serum amyloid A (SAA) binds to murine mast cells, and that SAA bound to connective tissue matrix induces adhesion of mast cells to both this matrix and to laminin, helping to regulate mast cell recruitment at extravascular inflammatory sites. Second, we have found that aggregated IgG signals mast cells to adhere to components of connective tissue matrix through FcgRIII. Recognition of this previously unknown biologic function for this receptor on mast cells provides a mechanism for the mast cell accumulation observed at sites of immune complex-dependent inflammation.
| Bandara, Geethani; Beaven, Michael A; Olivera, Ana et al. (2015) Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol 45:3034-44 |
| Kulka, Marianna; Fukuishi, Nobuyuki; Metcalfe, Dean D (2009) Human mast cells synthesize and release angiogenin, a member of the ribonuclease A (RNase A) superfamily. J Leukoc Biol 86:1217-26 |
| Metcalfe, Dean D (2008) Mast cells and mastocytosis. Blood 112:946-56 |
| Swindle, Emily J; Metcalfe, Dean D (2007) The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes. Immunol Rev 217:186-205 |
| Kushnir-Sukhov, Nataliya M; Brown, Jared M; Wu, Yalin et al. (2007) Human mast cells are capable of serotonin synthesis and release. J Allergy Clin Immunol 119:498-9 |
| Brown, Jared M; Swindle, Emily J; Kushnir-Sukhov, Nataliya M et al. (2007) Silica-directed mast cell activation is enhanced by scavenger receptors. Am J Respir Cell Mol Biol 36:43-52 |
| Sundstrom, J Bruce; Ellis, Jane E; Hair, Gregory A et al. (2007) Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood 109:5293-300 |
| Soule, Benjamin P; Brown, Jared M; Kushnir-Sukhov, Nataliya M et al. (2007) Effects of gamma radiation on FcepsilonRI and TLR-mediated mast cell activation. J Immunol 179:3276-86 |
| Carter, Melody C; Robyn, Jamie A; Bressler, Peter B et al. (2007) Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol 119:1550-1 |
| Prussin, Calman; Metcalfe, Dean D (2006) 5. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 117:S450-6 |
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