The IgE-mediated secretory response of sensitized basophils or mast cells to appropriate antigen is the initiating event of immediate hypersensitivity reactions. It is now recognized that the variety of mediators released during this process induce development of a localized inflammatory response. These inflammatory events are responsible for the amplification of allergic reactions and, if potentiated or prolonged, the development of allergic disease states. Therefore, elucidation of the mechanisms for the amplification or prolongation of allergic reactions is important to an understanding of the pathogenesis of atopic disease. A potentially important mechanism is potentiation or prolongation of basophil and mast cell secretory processes by reactants generated during the inflammatory events. Using human basophils, three potential influences on the secretory process have been identified. (1) Complexed or surface-bound IgG potentiates IgE-mediated histamine release. (2) Major basic protein isolated from human eosinophil granule stimulates IgE-independent histamine release. (3) The model basic polypeptide protamine potentiates IgE-mediated histamine release. It is postulated that similar interactions in vivo may constitute important mechanisms for the amplification and prolongation of allergic reactions involving human basophils. The project has four goals. (1) Establish the participation of basophil Fc(IgG) receptors and basophil 5-lipoxygenase metabolites in the enhancement mechanism by complexed or surface-bound IgG. (2) Determine the mechanism and binding moiety for major basic protein-stimulated histamine release. (3) Determine the mechanism for enhancement by basic polypeptides and identify basic polypeptides associated with allergic and inflammatory reactions that may potentiate IgE-mediated release. (4) Extend the above influences to the release of additional basophil mediators, particularly lipoxygenase and cyclo-oxygenase products.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017177-05
Application #
3127020
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-08-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
5
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612
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Golightly, L M; Thomas, L L; Dvorak, A M et al. (1992) Charcot-Leyden crystal protein in the degranulation and recovery of activated basophils. J Leukoc Biol 51:386-92
Moy, J N; Gleich, G J; Thomas, L L (1990) Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. J Immunol 145:2626-32
Anselmino, L M; Perussia, B; Thomas, L L (1989) Human basophils selectively express the Fc gamma RII (CDw32) subtype of IgG receptor. J Allergy Clin Immunol 84:907-14
Thomas, L L; Zheutlin, L M; Gleich, G J (1989) Pharmacological control of human basophil histamine release stimulated by eosinophil granule major basic protein. Immunology 66:611-5
Espiritu, B R; Szpindor-Watson, A; Zeitz, H J et al. (1988) IgE-mediated sensitivity to Trichophyton rubrum in a patient with chronic dermatophytosis and Cushing's syndrome. J Allergy Clin Immunol 81:847-51
Schmeichel, C J; Thomas, L L (1987) Methylxanthine bronchodilators potentiate multiple human neutrophil functions. J Immunol 138:1896-903
Tobin, M C; Karns, B K; Anselmino, L M et al. (1986) Potentiation of human basophil histamine release by protamine: a new role for a polycation recognition site. Mol Immunol 23:245-53
Pendy, L M; Arra, S J; Anselmino, L M et al. (1986) A flow cytometric procedure for the isolation of antigenically responsive human basophils. J Immunol Methods 91:59-63