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.
