Methods of identifying compounds that modulate igg mediated mast cell activation
The present invention relates to methods for identifying compounds capable of modulating Fcg receptor signaling pathway in mast and/or basophil cells. The invention further relates to methods for identifying compounds for use as therapeutic agents in the treatment of disorders related to activation of Fcg receptor signaling cascade.
1 . A method of identifying a compound capable of modulating Fcγ receptor signaling pathway, comprising
a) contacting at least one IgE primed mast cell with a candidate compound in the presence of Fcγ receptor signaling activation; and
b) determining whether the candidate compound modulates the Fcγ receptor-mediated signaling cascade.
2 . The method of claim 1 in which the candidate compound inhibits the Fcγ receptor signaling cascade.
3 . The method of claim 1 in which the Fcγ receptor is FcγRI.
4 . The method of claim 1 in which the mast cell is a cultured mast cell.
5 . The method of claim 1 in which the mast cell is a mucosal mast cell.
6 . The method of claim 1 in which the mast cell is a human mast cell.
7 . The method of claim 1 in which the modulation of Fcγ receptor signaling cascade is determined by measuring degranulation.
8 . The method of claim 7 in which the modulation of Fcγ receptor signaling is determined by comparing Fcγ receptor-mediated mast cell activation in presence and absence of the candidate compound.
9 . The method of claim 1 in which the compound is a small organic compound.
10 . The method of claim 9 in which the small organic compound has a molecular weight in the range of about 100-2500 daltons.
11 . A method of identifying a compound for treating disorders of IgG-mediated mast cell activation, comprising:
a) contacting at least one IgE primed mast cell with a candidate compound in the presence of Fcγ receptor signaling activation; and
b) determining whether the candidate compound modulates the Fcγ receptor signaling cascade.
12 . The method of claim 11 in which the candidate compound inhibits the Fcγ receptor signaling cascade.
13 . The method of claim 11 in which the Fcγ receptor is FcγRI.
14 . The method of claim 11 in which the mast cell is a cultured mast cell.
15 . The method of claim 11 in which the mast cell is a mucosal mast cell.
16 . The method of claim 11 in which the mast cell is a human mast cell.
17 . The method of claim 11 in which modulation of the Fcγ receptor signaling cascade is determined by measuring degranulation.
18 . The method of claim 11 in which modulation of the Fcγ receptor signaling cascade is determined by comparing Fcγ receptor-mediated mast cell activation in presence and absence of the candidate compound.
19 . The method of claim 11 in which the compound is a small organic compound.
20 . The method of claim 19 in which the small organic compound has a molecular weight in the range of about 100-2500 daltons.
21 . A method of identifying a compound capable of modulating IgE priming of mast cells, comprising:
a) contacting at least one mast cell with a candidate compound and priming the mast cell with IgE antibody,
b) activating signal transduction via Fcγ receptor-mediated signaling pathway, and
c) determining whether the candidate compound modulates IgE priming of the mast cell.
22 . The method of claim 21 in which the candidate compound inhibits IgE priming of the mast cell.
23 . The method of claim 21 in which the Fcγ receptor is FcγRI.
24 . The method of claim 21 in which the mast cell is a cultured mast cell.
25 . The method of claim 21 in which the mast cell is a mucosal mast cell.
26 . The method of claim 21 in which the mast cell is a human mast cell.
27 . The method of claim 21 in which modulation of the IgE priming of the mast cell is determined by measuring degranulation.
28 . The method of claim 21 in which modulation of the IgE priming of mast cell is determined by comparing IgE priming in presence and absence of the candidate compound.
29 . The method of claim 21 in which the compound is a small organic compound.
30 . The method of claim 29 in which the small organic compound has a molecular weight in the range of about 100-2500 daltons.