Pulmonary granulomatous hypersensitivity reactions (e.g., to invasive parasites) may cause a dramatic stimulation of eosinophil production and local accumulation but eosinophil functions in these reactions are unknown. It has been suggested that these cells may assist in the cytotoxic destruction of the parasite or alternatively that they may be homeostatic cells and serve to suppress the vigorous inflammatory reaction and minimize unnecessary damage to host tissues. This investigation will define the roles of eosinophils in such responses through the following approaches: 1) Examine destruction of newborn and muscle stage trichinella larvae in vitro: Morphologic study of development of pulmonary, peritoneal, or subcutaneous granulomata around larvae administered intravenously, intraperitoneally, or subcutaneously. Determine distribution of inflammatory cells within granulomata, in particular specific cells interacting directly with larvae. Examine timing, sequence, and site of activation of eosinophil lysosomal enzymes and subsequent degranulation by EM cytochemistry. Recover larvae from granulomata to determine kinetics of larval destruction as judged by morphology, motility, infectivity, and ability to incorporate 3H-2-deoxyglucose. 2) Examine cytotoxic reactions of controlled mixtures of purified effector cells (eosinophils, neutrophils, macrophages, lymphocytes; with and without antibody and complement) against trichinella larvae in vitro. Examine cytotoxic ability of purified human eosinophils and neutrophils obtained from normal and chronic granulomatous disease patients. 3) Develop models of parasite destruction employing target cells (mastocytoma cells, fibroblasts) coated with trichinella antigens. Examine cytotoxicity of effector cells against antigen-coated target cells. 4) Examine whether eosinophils amplify or suppress lymphocyte and macrophage cytotoxicity in the in vitro models. 5) Determine whether effects observed with intact cells can be duplicated using eosinophil lysosomal enzymes alone or with hydrogen peroxide and halide in a manner designed to mimic the eosinophil oxidative metabolic response.
Showing the most recent 10 out of 16 publications
