IMMUNOREGULATION OF THE SCHISTOSOME EGG GRANULOMA

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This search project comprises the continued elucidation of the inflammatory, immunoregulatory and reparative aspects of the parasite egg-induced granulomas in murine schistosomiasis mansoni. Our long term objective is to elucidate the dynamics of cell-cell interation, idnetify and define the function of molecular mediators and enzymes which participate in the evolution and involution of thegranulomatous response. A better understanding of the regulation of inflammation, tissue damage and healing in the murine model will greatly improve the clinical handling of schistosomiasis. The research objectives are divided into 4 interrelated areas: I. Analysis of T cell circuitry active in the immunomodulation of the granuloma. This will be carried out with isolated subpopulations of splenic and granuloma T lymphocytes, Adoptive cell transfers, in vitro cell-cell interactions, the production and functional examination of soluble regulatory/amplifier molecules will be employed. II. Studies on the accessory/regulatory role of granuloma macrophages. Macrophages will be isolated from vigorous and modulated granulomas and their accessory role in the elicitation of SEA-specific secondary immune response will be examined. Production of activating and inhibitory substances by these macrophages will be tested. III. Studies on the presence and role of angiotensins I, II and prostaglandins in the granulomatous response. Vigorous and modulated granulomas will be assayed for the presence of angiotensins and prostaglandins which may play important roles in the inflammatory/regulatory aspects of the granulomatous response. The effect of immunomanipulationon the levels of these substances within the granulomas will be assayed. IV. Studies on the effect of immunomaipulation on liver collagen content and breakdown. Liver and granuloma collagen content as well as the presence of degradative neutral proteases in the virorous or modulated granulomas will be examined. The source of neutral proteases within the lesions will be localized. The class of degradative enzymes and their potential inhibitors will be identified. The effect of immunomanipulation on total collagen content, and activity of collagenease, elastase enzymes will be examined.