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. 1981 Mar 1;153(3):520–533. doi: 10.1084/jem.153.3.520

Mast cell-mediated tumor-cell cytotoxicity. Role of the peroxidase system

PMCID: PMC2186115  PMID: 7252407

Abstract

Mast cells, when supplemented with H2O2 and iodide, are cytotoxic to mammalian tumor cells as determined by 51Cr release, and transmission and scanning electron microscopy. H2O2 at the concentration employed (10(-4) M) initiates mast cell degranulation, and mast cell granules (MCG), which contain a small amount of endogenous peroxidase activity, are toxic to tumor cells when combined with H2O2 and iodide. This toxicity is greatly increased by binding eosinophil peroxidase (EPO) to the MCG surface. Each component of the mast cell, MCG, or MCG-EPO system was required and toxicity was inhibited by the addition of the hemeprotein inhibitors azide or aminotriazole, which is compatible with a requirement for peroxidase in the cytotoxic reaction. A sequence of reactions is proposed in which mast cells, stimulated to release their granules by H2O2 generated by adjacent phagocytes, react with H2O2 and a halide to damage tumor cells. EPO release from eosinophils may contribute to this sequence of reactions, both by stimulation of H2O2- induced mast cell secretion and by combination with MCG to form a complex with augmented tumoricidal activity. These rections may play a role in the host defense against neoplasms.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baehner R. L., Johnston R. B., Jr Metabolic and bactericidal activities of human eosinophils. Br J Haematol. 1971 Mar;20(3):277–285. doi: 10.1111/j.1365-2141.1971.tb07038.x. [DOI] [PubMed] [Google Scholar]
  2. Bowers H. M., Jr, Mahapatro R. C., Kennedy J. W. Numbers of mast cells in the axillary lymph nodes of breast cancer patients. Cancer. 1979 Feb;43(2):568–573. doi: 10.1002/1097-0142(197902)43:2<568::aid-cncr2820430225>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  3. Clark R. A., Klebanoff S. J., Einstein A. B., Fefer A. Peroxidase-H2O2-halide system: Cytotoxic effect on mammalian tumor cells. Blood. 1975 Feb;45(2):161–170. [PubMed] [Google Scholar]
  4. Combs J. W., Purnell D. M. Functional characteristics of mast cells associated with rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. J Natl Cancer Inst. 1973 Apr;50(4):1003–1011. doi: 10.1093/jnci/50.4.1003. [DOI] [PubMed] [Google Scholar]
  5. Cotran R. S., Litt M. The entry of granule-associated peroxidase into the phagocytic vacuoles of eosinophils. J Exp Med. 1969 Jun 1;129(6):1291–1306. doi: 10.1084/jem.129.6.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dvorak A. M., Galli S. J., Galli A. S., Hammond M. E., Churchill W. H., Jr, Dvorak H. F. Tumor-basophil interactions in vitro--a scanning and transmission electron microscopic study. J Immunol. 1979 Jun;122(6):2447–2457. [PubMed] [Google Scholar]
  7. Dvorak H. F., Dvorak A. M., Churchill W. H. Immunologic rejection of diethylnitrosamine-induced hepatomas in strain 2 guinea pigs: participation of basophilic leukocytes and macrophage aggregates. J Exp Med. 1973 Mar 1;137(3):751–775. doi: 10.1084/jem.137.3.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edelson P. J., Cohn Z. A. Peroxidase-mediated mammalian cell cytotoxicity. J Exp Med. 1973 Jul 1;138(1):318–323. doi: 10.1084/jem.138.1.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FISHER E. R., FISHER B. ROLE OF MAST CELLS IN TUMOR GROWTH. Arch Pathol. 1965 Feb;79:185–191. [PubMed] [Google Scholar]
  10. Graham R. M., Graham J. B. Mast cells and cancer of the cervix. Surg Gynecol Obstet. 1966 Jul;123(1):3–9. [PubMed] [Google Scholar]
  11. Henderson W. R., Chi E. Y., Klebanoff S. J. Eosinophil peroxidase-induced mast cell secretion. J Exp Med. 1980 Aug 1;152(2):265–279. doi: 10.1084/jem.152.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henderson W. R., Jong E. C., Klebanoff S. J. Binding of eosinophil peroxidase to mast cell granules with retention of peroxidatic activity. J Immunol. 1980 Mar;124(3):1383–1388. [PubMed] [Google Scholar]
  13. Henderson W. R., Kaliner M. Mast cell granule peroxidase: location, secretion, and SRS-A inactivation. J Immunol. 1979 Apr;122(4):1322–1328. [PubMed] [Google Scholar]
  14. Jong E. C., Henderson W. R., Klebanoff S. J. Bactericidal activity of eosinophil peroxidase. J Immunol. 1980 Mar;124(3):1378–1382. [PubMed] [Google Scholar]
  15. Jong E. C., Klebanoff S. J. Eosinophil-mediated mammalian tumor cell cytotoxicity: role of the peroxidase system. J Immunol. 1980 Apr;124(4):1949–1953. [PubMed] [Google Scholar]
  16. Klebanoff S. J., Durack D. T., Rosen H., Clark R. A. Functional studies on human peritoneal eosinophils. Infect Immun. 1977 Jul;17(1):167–173. doi: 10.1128/iai.17.1.167-173.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McLaren D. J., Mackenzie C. D., Ramalho-Pinto F. J. Ultrastructural observations on the in vitro interaction between rat eosinophils and some parasitic helminths (Schistosoma mansoni, Trichinella spiralis and Nippostrongylus brasiliensis). Clin Exp Immunol. 1977 Oct;30(1):105–118. [PMC free article] [PubMed] [Google Scholar]

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