Eosinophilia is a frequent concomitant of allergic and certain related immunologic responses. To elucidate the role of the human eosinophilic leukocyte in these responses, we will investigate several interrelated aspects of the cellular functioning of human eosinophils. The biochemical and functional properties of selected, homogeneously purified eosinophil proteins (including lysophospholipase, eosinophil peroxidase, and histaminase) will be studied. Eosinophil chemoattractant lymphokines produced by antigen, mitogen and histamine stimulated human blood mononuclear cells will be purified; the lymphokine producing cells will be characterized and the effects of the purified lymphokines on eosinophil migration, activation and poiesis will be assessed. Utilizing electron microscopy and sensitive radioimmunoassays developed for various granular and extragranular human eosinophil proteins, the mechanisms of extracellular secretion of these proteins from eosinophils will be determined, and in conjunction with subcellular fractionation, the intracellular compartmentalization of these constituents will be determined. Possible proteins synthesized by these stimulated eosinophils will be investigated and their activities on other cell types (lymphocytes, fibroblasts, granulocytes) assessed. We hope to elucidate mechanisms of eosinophil functioning in tissues during allergic and immunologic responses and to define mechanisms whereby mast-cell released histamine, acting via the elaboration of eosinophil-active lymphocyte products, may not only lead to prolonged tissue eosinophilia but also to increased eosinophilpoiesis, to activation of tissue eosinophils and possibly to collaboration of eosinophils with other cells types. With these studies, an integrated understanding of the genesis, accumulation and functions of eosinophils at sites of allergic responses may develop that will guide the rational therapy of these allergic responses.
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