The program is composed of two disease-oriented subsections, pulmonary and dermatologic, which are integrated through mutual focus upon two cell types, the mast cell and the eosinophil, their products and diseases which likely result from the dys-regulation of their tissue phenotype and phlogistic potential mediated directly or via additional cell types. A particular program is to transfer the current understanding of pathobiology of bronchial asthma and its treatment to urban minority populations through a demonstration and education project with assessment of benefit. Culturally appropriate educational programs will be targeted to both patients with asthma and their personal physicians to increase their understanding of the pathobiology of this disease and the importance of objective monitoring of lung function through the use of home peak flow measurements and Health Center based spirometry. In the pulmonary subsection, the urinary excretion of LTE4 will be used as an index of the endogenous production of the cysteinyl leukotrienes in normal subjects with induced airway hyper-responsiveness and in patients with bronchial asthma as a possible index of disease activity or of distinct pathobiologic subgroups. The presence of tissue and circulating cytokines capable of altering the eosinophil phenotype so as to augment viability and prime for ligand mediated responses will be sought not only in chronic eosinophilic pneumonia but also in bullous pemphigoid. The regulation of expression of beta-glucan receptors on monocyte/macrophages in allergic bronchopulmonary aspergillosis will be assessed relative to uninfected patients and the effects of treatment with corticosteroids. Discriminatory anti-peptide antibodies and molecular probes directed against a panel of human mast cell proteases will be prepared and used to analyze mast cell maturation in vitro, utilizing insights and systems gained from parallel studies in the mouse mast cell system. Of particular note is that these probes will be used to phenotype human mast cells in normals and at normal and lesional sites of patients with physical allergies (exercise-associated anaphylaxis, cold-induced urticaria, dermographism, and cholinergic urticaria), systemic mastocytosis, and bullous pemphigoid. As the number of discriminatory probes increases, it is anticipated that the phenotyping of mast cells, along with ultrastructural analysis of granule structure and cell distribution, may reveal the pathobiologic importance of various phenotypes while also providing insight into the role of the tissue site in the regulation of phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI031599-03
Application #
3547844
Study Section
Special Emphasis Panel (SRC (86))
Project Start
1991-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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
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; 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
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

Showing the most recent 10 out of 14 publications