In chronic schistosomiasis mansoni the major pathologic lesions are granulomas surrounding eggs deposited in host tissues. Parasite ova release antigenic material that sensitize the host, resulting in the development of delayed-type hypersensitivity granulomas. The objectives of the present study were to assess the ability of components of the host granulomatous response to induce biochemical and biologic alterations in eggs in vitro, and to correlate these with the capacity of ova to induce granulomas in vivo. An assay of egg tricarboxylic acid cycle activity was developed by use of 2-[14C]acetate as substrate and measurement of accumulation of released 14CO2. Addition of human granulocytes (96% neutrophils, 4% eosinophils) to eggs (cell/egg ratio 1,000:1) and heat-inactivated normal human serum reduced predicted egg 14CO2 generation by 15.6 +/- 3.0%. This effect was greater in the presence of sera of subjects with schistosomiasis (25.6 +/- 2.8% reduction) or when complement was present (24.4 +/- 4.0%). Autologous eosinophils and neutrophils were equally effective in decreasing egg 2-[14C]acetate metabolism (25.6 and 21.4% reductions, respectively). Since the biological role of schistosome eggs relates to their ability to hatch and produce miracidia, we evaluated the effect of granulocytes and sera on this function. The hatching rate of eggs incubated with normal serum was 52.8 +/- 3.3 miracidia/100 eggs; this value decreased to 37.0 +/- 2.6 when granulocytes were added (P less than 0.01). Granulocytes plus antibody- or complement-containing sera led to hatching rates of 23 and 20 miracidia/100 eggs. When ova were pre-incubated with granulocytes and various sera and injected into mice, the areas of egg-induced pulmonary granulomas measured 8 d later were reduced 32 to 45% as compared with lesions elicited by parasite eggs not exposed to granulocytes. Exposure of antigen-coated Sepharose beads to granulocytes and immune serum before injection into mice also led to a reduction in granuloma formation as compared with beads pre-incubated with serum alone. These data indicate that granulocytes in conjunction with antibodies and complement inflict biologically relevant toxic effects on eggs that are manifest in vivo by a decreased ability to elicit granulomas.
P A de Brito, J W Kazura, A A Mahmoud