This proposal outlines a four project program designed to meet the requirements for an Asthma, Allergy and Immunologic Diseases Cooperative Research Center (AAIDCRC). The basic science component of this proposal brings together three internationally recognized scientists, Jean-Pierre Kinet, M.D, Stephen J. GalIi M.D., and Peter F. Weller M.D., with established records of individual and collaborative productivity, each of whom will direct a project investigating high affinity IgE receptor-dependent processes which are relevant to the pathogenesis of asthma. The three projects: project 1-IgE Regulation of Fc epsilon RI: Modulation and Significance; project 2-Anti-FcepsilonRI alpha Autoantibodies in Asthma; and project 3- Airway Eosinophils As Antigen-Presenting Cells in Asthma, are united by a central theme: evaluating the possibility that the high affinity IgE receptor (FcepsilonRI) represents a hitherto unsuspected link between the pathogenesis of """"""""allergic"""""""" and """"""""non-allergic"""""""" forms of asthma, and that this receptor, in addition to triggering the release of-mediators and cytokines from FcepsilonRI+ effector cells, may also mediate other functions which contribute to the initiation and perpetuation of asthmatic responses. In addition, each project will utilize a common novel murine model, """"""""FcepsilonRI-humanized"""""""" mice (described herein) for many of its studies. The synergistic aspects of these projects are a strong rationale for their being funded through an AAIDCRC, which will enhance the opportunities for creative interactions among the participating investigators. In addition to the basic scientific components, this proposal includes a Demonstration and Education Project which will directed by an internationally known researcher in the areas of child health policy and adjustment to childhood chronic illness, James M. Perrin, M.D. This project will examine the impact on measures of asthma morbidity (hospitalization, emergency room and physician/nurse visits, and school participation) of a culturally-sensitive, age-appropriate, cooperative asthma management educational program for children with asthma and their parents. The study, which will be conducted in a high-risk urban community (Chelsea, MA), will, in all phases, examine several child and illness-specific, family, health systems, and environmental variables and will assess the extent to which they predict morbidity from asthma. It will also assess several variations in the site and type of education, and in clinical and demographic characteristics of children and households, and determine whether they affect the benefit of the educational interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI041995-03
Application #
2887608
Study Section
Special Emphasis Panel (ZAI1-ACS-I (O1))
Program Officer
Adams, Ken
Project Start
1997-09-30
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Wang, Hai-Bin; Ghiran, Ionita; Matthaei, Klaus et al. (2007) Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol 179:7585-92
Gotlib, Jason; Berube, Caroline; Growney, Joseph D et al. (2005) Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood 106:2865-70
Maurer, Marcus; Galli, Stephen J (2004) Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor. Lab Invest 84:1593-602
Tedla, Nicodemus; Bandeira-Melo, Christianne; Tassinari, Paolo et al. (2003) Activation of human eosinophils through leukocyte immunoglobulin-like receptor 7. Proc Natl Acad Sci U S A 100:1174-9
Bandeira-Melo, Christianne; Woods, Lesley J; Phoofolo, Mojabeng et al. (2002) Intracrine cysteinyl leukotriene receptor-mediated signaling of eosinophil vesicular transport-mediated interleukin-4 secretion. J Exp Med 196:841-50
Sayama, Koichi; Diehn, Maximilian; Matsuda, Kentaro et al. (2002) Transcriptional response of human mast cells stimulated via the Fc(epsilon)RI and identification of mast cells as a source of IL-11. BMC Immunol 3:5
Bandeira-Melo, Christianne; Hall, John C; Penrose, John F et al. (2002) Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human eosinophils. J Allergy Clin Immunol 109:975-9
Asai, K; Kitaura, J; Kawakami, Y et al. (2001) Regulation of mast cell survival by IgE. Immunity 14:791-800
Bandeira-Melo, C; Sugiyama, K; Woods, L J et al. (2001) Cutting edge: eotaxin elicits rapid vesicular transport-mediated release of preformed IL-4 from human eosinophils. J Immunol 166:4813-7
Bandeira-Melo, C; Phoofolo, M; Weller, P F (2001) Extranuclear lipid bodies, elicited by CCR3-mediated signaling pathways, are the sites of chemokine-enhanced leukotriene C4 production in eosinophils and basophils. J Biol Chem 276:22779-87

Showing the most recent 10 out of 17 publications