Symptoms of immediate hypersensitivity result from the release of histamine and other chemicals from several cell types, including basophils. Mediator release is not an all-or-none phenomenon. Intrinsic differences in releasability have been documented previously. We have shown in preliminary studies that extrinsic agents can influence mediator release as well. We have designed experiments to investigate the ability of a variety of immunologically active biologic molecules to modulate the activation of human peripheral blood basophils, using histamine release as an endpoint. Specifically, we will examine the extrinsic modulation of histamine release in vitro in the presence of: a) bacterial lipopolysaccharides and yeast cell walls; b) immunoglobulins and serum albumin; and c) lysolecithins and lectins contained in well-recognized food allergens. By doing so, we intend to: (1) establish the experimental concept of extrinsic modulation of histamine release from human basophils; (2) begin experiments to delineate potential molecular mechanisms for this phenomenon; (3) explore the clinical relevance of this concept by examining the relative extent of modulation of release from basophils from allergic donors in comparison to controls. Selective modulation by certain materials may explain the clinical significance of some allergens and infectious agents, and selective sensitivity of individuals may explain their experiencing clinical symptoms. Host responses may also down-regulate mediator release. Extrinsic modulation may be fundamental to regulation of cell activation as well as to clinical expression of allergy, and an understanding of the basis of the phenomenon may permit logical intervention to modify or prevent allergic symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
5R23AI021072-02
Application #
3445534
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Smith, T F; Sanchez-Legrand, F; McKean, L P et al. (1992) Role of sodium in mediator release from human basophils. J Allergy Clin Immunol 89:978-86
Smith, T F; Bain, R P; Schiffman, G (1990) Relationship between serum IgG2 concentrations and antibody responses to pneumococcal polysaccharides in children with chronic chest symptoms. Clin Exp Immunol 80:339-43
Sanchez-Legrand, F; Smith, T F (1989) Interaction of paramyxoviruses with human basophils and their effect on histamine release. J Allergy Clin Immunol 84:538-46
Atkinson, T P; Smith, T F; Hunter, R L (1988) In vitro release of histamine from murine mast cells by block co-polymers composed of polyoxyethylene and polyoxypropylene. J Immunol 141:1302-6
Atkinson, T P; Smith, T F; Hunter, R L (1988) Histamine release from human basophils by synthetic block co-polymers composed of polyoxyethylene and polyoxypropylene and synergy with immunologic and non-immunologic stimuli. J Immunol 141:1307-10
Atkinson, T P; Bullock, J O; Smith, T F et al. (1988) Ion transport mediated by copolymers composed of polyoxyethylene and polyoxypropylene. Am J Physiol 254:C20-6
Smith, T F; Morrison, D C (1986) Lack of interference in skin tests by endotoxin in allergen extracts. Ann Allergy 57:410-2