During this reporting period, in collaborative efforts, we have continued to explore the control of mast cell function by stem cells and completed the characterization of N-linked glycans in human mast cells, and reported the role of human mast cells in the detection of dengue virus. We have now reported an interaction between mast cells and bone marrow-derived stem cells (BMSCs). Mast cell degranulation, cytokine production and chemotaxis were evaluated in vitro following co-culture with BMSCs. We found that stromal cells will effectively suppress specific mast cell degranulation, pro-inflammatory cytokine production and chemotaxis. Mast cell degranulation within mouse skin or the peritoneal cavity was similarly suppressed following in vivo administration of stromal cells. These inhibitory effects were for the large part dependent upon up-regulation of COX2 in BMSCs and were facilitated through the activation of EP4 receptors on MCs. Similarly, we and our collaborators completed an examination of the the glycomes of key effector cells in allergic inflammation including eosinophils, basophils, and mast cells. This was done to help elucidate the contribution of carbohydrates to the induction and regulation of allergic inflammatory responses. Results revealed substantive quantities of terminal GlcNAc containing structures in both the eosinophil and basophil samples. In contrast, mast cells displayed greater relative quantities of sialylated terminal epitopes. These cell surface glycan structures through interaction with lectins may help regulate cellular functions and thus have implications for the pathogenesis of allergic diseases.

Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2012
Total Cost
$220,824
Indirect Cost
City
State
Country
Zip Code
Valent, Peter; Akin, Cem; Arock, Michel et al. (2012) Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 157:215-25
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Brown, J M; Nemeth, K; Kushnir-Sukhov, N M et al. (2011) Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism. Clin Exp Allergy 41:526-34
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Gilfillan, Alasdair M; Austin, Sarah J; Metcalfe, Dean D (2011) Mast cell biology: introduction and overview. Adv Exp Med Biol 716:2-12
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Stone, Kelly D; Prussin, Calman; Metcalfe, Dean D (2010) IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 125:S73-80
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Gilfillan, Alasdair M; Peavy, Richard D; Metcalfe, Dean D (2009) Amplification mechanisms for the enhancement of antigen-mediated mast cell activation. Immunol Res 43:15-24

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