Laboratory of Allergic Diseases

Mast Cell Biology Section

Description of Research Program

The mast cell is the focus of the Mast Cell Biology Section (MCBS) research effort. This multifunctional inflammatory cell is involved in both innate and acquired immunity and plays a central role in the induction of allergic inflammation. An integrated program investigating mast cell biology includes studies into the growth and differentiation of mast cells, mast cell signal transduction, and the products generated by mast cells that lead to disease. Emphasis is on basic research that may be translated into the clinic, where protocols include studies on the pathogenesis of asthma and systemic mast cell disorders, including mastocytosis and anaphylaxis. Research efforts have contributed to the identification of mutations in the receptor for stem cell factor, understanding signaling through high affinity IgE and IgG receptors, and the demonstration of regulation of tissue mast cell number through programmed cell death.

• Further characterization of mast cell precursors
• Characterization of signaling pathways in human mast cells
• Examination of the role of mast cells in innate immunity
• Characterization of new and novel mast cell mediators
• Application of this information to the diagnosis and treatment of asthma and other allergic and immunologic diseases

Selected Recent Publications

To view a complete listing, visit PubMed.

D’Ambrosio C, Akin C, Wu Y, Magnusson MK, Metcalfe DD. Gene expression analysis in mastocytosis reveals a highly consistent profile with candidate molecular markers. J Allergy Clin Immunol. 2003. 112: 1162-1170.

Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD. A novel form of mastocytosis associated with transmembrane c-Kit mutation and response to imatinib. Blood. 2004. 103: 3222-3225.

Tkaczyk C, Horejsi V, Iwaki S, Draber P, Samelson LE, Nahm D-H, Metcalfe DD, Gilfillan AM. NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and FceRI aggregation. Blood. 2004. 104: 207-214.

Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD. Activation of mast cells by double-stranded RNA: evidence for activation through toll-like receptor-3 (TLR-3). J Allergy Clin Immunol. 2004. 114: 174-182.

Taylor ML, Sehgal D, Raffeld M, Obiakor H, Akin C, Mage RG, Metcalfe DD. Demonstration that mast cells, T cells and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis. J Mol Diagn. 2004. 6: 335-342.

Davis BJ, Flanagan BF, Gilfillan AM, Metcalfe DD, Coleman JW. Nitric oxide inhibits IgE-dependent cytokine production and Fas and Jun activation in mast cells. J Immunol. 2004. 173: 6914-6920.

Kulka M, Metcalfe DD. High resolution tracking of cell division demonstrates differential effects of TH-1 and TH-2 cytokines on SCF-dependent human mast cell production in vitro: correlation with apoptosis and Kit expression. Blood. 2004. 105: 592-599.

Swindle EJ, Metcalfe DD, Coleman JW. Rodent and human mast cells produce functionally significant intracellular reactive oxygen species, but not nitric oxide. J Biol Chem. 2004. 279: 48751-48759.

Iwaki S, Tkaczyk C, Satterthwaite AB, Halcomb K, Beaven MA, Metcalfe DD, Gilfillan AM. Btk plays a crucial role in the amplification of antigen-dependent mast cell activation by Kit. J Biol Chem. 2005. 280: 40261-40270.

Gilfillan AM, Tkaczyk C. Integrated signaling pathways for mast cell activation. Nature Rev Immunol. 2006. 6(3): 218-230.

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