The investigator has recently demonstrated that FceRI expression can be both down-regulated and up-regulated on human basophils and appears to be regulated by the IgE antibody. The receptor through which this regulation occurs is unknown, although FceRI or FceRII are reasonable candidates.
The first aim addresses the question of whether FceRI expression is regulated in a similar manner in patients with various clinical conditions and whether it is regulated also on mast cells and monocytes in a similar manner.
The second aim addresses some issues related to the mechanism of FceRI expression, focusing on the determination of whether there are coordinated changes in the FceRI-beta and -gamma subunits as well as closely associated tyrosine kinases. The functional consequences of FceRI up-regulation will be studied and pharmacological agents that regulate FceRI expression will be explored.
The third aim focuses on determining the receptor involved in IgE-mediated FceRI upregulation. Whether receptor upregulation is associated with increased FceRI mRNA accumulation and the how the promoters for the receptor genes are regulated will also be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI042220-03
Application #
6149865
Study Section
Special Emphasis Panel (ZRG2-IMS (01))
Program Officer
Plaut, Marshall
Project Start
1998-02-01
Project End
2001-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
3
Fiscal Year
2000
Total Cost
$219,983
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Saini, S S; Richardson, J J; Wofsy, C et al. (2001) Expression and modulation of FcepsilonRIalpha and FcepsilonRIbeta in human blood basophils. J Allergy Clin Immunol 107:832-41
Saini, S S; Klion, A D; Holland, S M et al. (2000) The relationship between serum IgE and surface levels of FcepsilonR on human leukocytes in various diseases: correlation of expression with FcepsilonRI on basophils but not on monocytes or eosinophils. J Allergy Clin Immunol 106:514-20
MacGlashan Jr, D; Lichtenstein, L M; McKenzie-White, J et al. (1999) Upregulation of FcepsilonRI on human basophils by IgE antibody is mediated by interaction of IgE with FcepsilonRI. J Allergy Clin Immunol 104:492-8