Basophils and mast cells are major effector cells of immediate hypersensitivity reactions. In humans, mast cell involvement can be precisely identified by the presence of tryptase. For basophils, no such direct marker has been identified. The investigator hypothesizes that human basophil secretory granule proteins can be used as sensitive and specific markers of basophil involvement and that understanding the functions of such proteins will further our understanding of this cell type. The 2D7 mAb prepared by the investigator appears to recognize a basophil-specific component of the secretory granule. In skin during the late phase of an immediate hypersensitivity response, 2D7 immunohistochemistry reveals marked basophil involvement.
Four specific aims are proposed. First, the 2D7 antigen will be purified by immunoaffinity chromatography and characterized. Second, basophils and deposits of activated basophils will be examined in human tissues using the 2D7 mAb, including skin in atopic dermatitis, chronic urticaria, and urticaria pigmentosa, nasal mucosa in allergic rhinitis and lung in asthma. Third, new mAbs against 2D7 antigen will be generated and used to develop a sandwich immunoassay. Fourth, basophil activation in various clinical situations will be assessed by measuring 2D7 antigen levels in biologic fluids. For example, the investigator hypothesizes that basophil-dependent anaphylaxis occurs in certain food-allergic reactions, and predict that 2D7 antigen, but not mast cell tryptase, will be elevated in the blood during such reactions. This research will provide novel and precise measures of basophil involvement in human diseases. This may enable more precise diagnostic criteria for flares of inflammation associated with atopic disease, facilitate selection of appropriate treatment, provide new prognostic information, and permit monitoring of inflammatory disease activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045441-04
Application #
6375139
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Plaut, Marshall
Project Start
1998-09-01
Project End
2002-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
2001
Total Cost
$203,499
Indirect Cost
Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Gomez, Gregorio; Schwartz, Lawrence; Kepley, Christopher (2007) Syk deficiency in human non-releaser lung mast cells. Clin Immunol 125:112-5
Cooper, Philip J; Schwartz, Lawrence B; Irani, Anne-Marie et al. (2002) Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin. J Infect Dis 186:1307-13
Foster, Barbara; Schwartz, Lawrence B; Devouassoux, Gilles et al. (2002) Characterization of mast-cell tryptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol 109:287-93
Sperr, W R; Stehberger, B; Wimazal, F et al. (2002) Serum tryptase measurements in patients with myelodysplastic syndromes. Leuk Lymphoma 43:1097-105
Sperr, W R; Jordan, J H; Baghestanian, M et al. (2001) Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. Blood 98:2200-9
Nouri-Aria, K T; Irani, A M; Jacobson, M R et al. (2001) Basophil recruitment and IL-4 production during human allergen-induced late asthma. J Allergy Clin Immunol 108:205-11
Bacon, A S; Ahluwalia, P; Irani, A M et al. (2000) Tear and conjunctival changes during the allergen-induced early- and late-phase responses. J Allergy Clin Immunol 106:948-54
Gauvreau, G M; Lee, J M; Watson, R M et al. (2000) Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics. Am J Respir Crit Care Med 161:1473-8