It has been known for sometime that mast cells residing in different tissue locations store their granules varied types and amounts of proteoglycans and neutral proteases. Although in vitro studies have given in sight as to which cytokines probably regulate mast cell granule heterogeneity in the BALB/c mouse, it has not been possible to address tissue-directed mast cell differentiation and maturation in this mouse strain. It also has not been possible to experimentally address the functional significance of granule heterogeneity in vivo. We have recently discovered that when an immature v-abl-transformed mouse mast cell line (V3-MC) is adoptively transferred into a BALB/c mouse, systemic mastocytosis develops rapidly in the liver, spleen, lung, and intestine. The long term objective of project 2 is to use the V3 mastocytosis mouse to study mast cell differentiation, maturation, and function;
three specific aims are proposed. Preliminary data indicate that the V3-MC that develop in the liver and intestine of this diseased mouse exhibit different granule phenotypes. Thus, protease specific antibodies and gene-specific probes will be used in specific aim 1 to investigate tissue-directed regulation of the differentiation and maturation processes of mast cells in V3 mastocytosis mice. Because fibrosis is usually associated with increased number of cells that morphologically resemble fibroblasts, the adoptive transfer system will be used in specific aim 2 to study mast-cell mediated fibrosis. V3-MC associated fibrosis in the liver and spleen of the mastocytosis mouse will be compared with non-fibrotic tissue in the animals to determine if a specific mast cell phenotype regulate host tissue responses. Mast cells contain substantially more neutral protease than any other cell in the body. However, it is not known what happens to these proteases when they are exocytosed from the mast cell in vivo. As assessed by SDS- PAGE/immunoblot analysis, high levels of mouse mast cell protease 7 are present in the blood 30 minutes after V3 mastocytosis mice are systemically activated with IgE and antigen. Thus in specific aim 3, the fate of the different granular constituents exocytosed from cultured V3- MC and from V3 mastocytosis mice with or without Fc-epsilon-RI perturbation will be investigated.

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Brigham and Women's Hospital
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Ohta, Shin; Imamura, Mitsuru; Xing, Wei et al. (2013) Group V secretory phospholipase A2 is involved in macrophage activation and is sufficient for macrophage effector functions in allergic pulmonary inflammation. J Immunol 190:5927-38
Giannattasio, Giorgio; Ohta, Shin; Boyce, Joshua R et al. (2011) The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonary inflammation. J Immunol 187:1486-95
Lundequist, Anders; Boyce, Joshua A (2011) LPA5 is abundantly expressed by human mast cells and important for lysophosphatidic acid induced MIP-1? release. PLoS One 6:e18192
Saino, Hiromichi; Ukita, Yoko; Ago, Hideo et al. (2011) The catalytic architecture of leukotriene C4 synthase with two arginine residues. J Biol Chem 286:16392-401
Laidlaw, Tanya M; Steinke, John W; Tinana, Adrienne M et al. (2011) Characterization of a novel human mast cell line that responds to stem cell factor and expresses functional FcýýRI. J Allergy Clin Immunol 127:815-22.e1-5
Giannattasio, Giorgio; Fujioka, Daisuke; Xing, Wei et al. (2010) Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function. J Immunol 185:4430-8
Lundequist, Anders; Nallamshetty, Samridhi N; Xing, Wei et al. (2010) Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation. J Immunol 184:433-41
Barrett, Nora A; Maekawa, Akiko; Rahman, Opu M et al. (2009) Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells. J Immunol 182:1119-28
Jones, Tatiana G; Hallgren, Jenny; Humbles, Alison et al. (2009) Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol 183:5251-60
Jiang, Yongfeng; Borrelli, Laura; Bacskai, Brian J et al. (2009) P2Y6 receptors require an intact cysteinyl leukotriene synthetic and signaling system to induce survival and activation of mast cells. J Immunol 182:1129-37

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