Mast cells have been demonstrated in increased numbers in certain neoplasms in humans (1-3) and in both spontaneous tumors and those induced by carcinogenic agents in animals (4, 5). Eosinophils are often closely associated with mast cells in inflammatory reactions, and these cells also are present in increased numbers in some neoplasms (6). The role of these inflammatory cells in the host defense against tumors is unknown.A number of distinct peroxidases exist in mammalian tissues which differ in primary structure and in their heme prosthetic group. When combined with H202 and a halide, peroxidases are toxic to a variety of targets including tumor cells. Peroxidases shown to have tumoricidal activity in vitro include the milk peroxidase (lactoperoxidase) (7), the neutrophil (and monocyte) peroxidase (myeloperoxidase) (8), and the eosinophil peroxidase (EPO) x (9). Mast cell granules (MCG) contain a small amount of peroxidase activity (10), and this activity is considerably increased by the firm binding of the positively charged EPO to the surface of the negatively charged MCG (11). H202 at relatively high concentrations can induce mast cell degranulation (12, 13). When the H202 concentration is lowered to a level where it is ineffective alone, noncytotoxic mast cell secretion is initiated on the supplementation of the H202 with EPO and a halide (14). We report here that mast cells are toxic to a line of mouse aseites lymphoma cells when combined with H202 and a halide. The H202 initiates mast cell secretion; the released granules with their endogenous peroxidase are toxic to the tumor cells in the presence of H202 and a halide. In addition, the binding of EPO to the MCG greatly potentiates their tumoricidal activity. Special Reagents. Compound 48/80, guaiacol (anhydrous), and Triton X-100 were obtained from Sigma Chemical Co., St. Louis, Mo.; glutaraldehyde from Polysciences, Inc., Warrington, Pa.; osmium tetroxide from Scientific Chemical Co., Huntington Beach, Calif.; and sodium chloride (Suprapur) was obtained from Matheson Coleman and Bell, Norwood, Ohio. All other reagents were of the highest commercial grade available. EPO was partially purified from
Materials and Methods
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