It is known that rodent mast cells respond to nerve growth factor (NGF). We have now shown that both the human mast cell line HMC-1 and cultured human mast cells similarly respond to NGF as evidenced by induction of the immediate early gene c-fos through the trkA tyrosine receptor which is phosphorylated on tyrosine residues following NGF exposure. HMC-1 and human mast cells were also found to express NGF mRNA and conditioned media from HMC-1 cells stimulated neurite outgrowth, an effect blocked by anti-NGF. Similarly, we identified the receptor for alpha-melanocyte stimulating hormone (alpha-MSH), MC-1, on murine mast cells. Treatment of mast cells with alpha-MSH increased cAMP levels and down-modulated expression of mRNA for IL-1beta, TNF-alpha, and lymphotactin in activated mast cells. In an animal model of asthma, we have characterized the resident cells responsible for immediate-early IL-4 production following antigen challenge.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Kulka, M; Metcalfe, D D (2006) TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol 43:1579-86
Metcalfe, Dean D; Boyce, Joshua A (2006) Mast cell biology in evolution. J Allergy Clin Immunol 117:1227-9
Kulka, Marianna; Fukuishi, Nobuyuki; Rottem, Menachem et al. (2006) Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation. J Leukoc Biol 79:339-50
Zudaire, Enrique; Martinez, Alfredo; Garayoa, Mercedes et al. (2006) Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. Am J Pathol 168:280-91
Davis, Beverley J; Flanagan, Brian F; Gilfillan, Alasdair M et al. (2004) Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun activation in mast cells. J Immunol 173:6914-20
Swindle, Emily J; Metcalfe, Dean D; Coleman, John W (2004) Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide. J Biol Chem 279:48751-9
Woolhiser, Michael R; Brockow, Knut; Metcalfe, Dean D (2004) Activation of human mast cells by aggregated IgG through FcgammaRI: additive effects of C3a. Clin Immunol 110:172-80
Kulka, Marianna; Alexopoulou, Lena; Flavell, Richard A et al. (2004) Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol 114:174-82
Basta, Milan; Van Goor, Fredric; Luccioli, Stefano et al. (2003) F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nat Med 9:431-8
Okayama, Yoshimichi; Tkaczyk, Christine; Metcalfe, Dean D et al. (2003) Comparison of Fc epsilon RI- and Fc gamma RI-mediated degranulation and TNF-alpha synthesis in human mast cells: selective utilization of phosphatidylinositol-3-kinase for Fc gamma RI-induced degranulation. Eur J Immunol 33:1450-9

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