Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells
- 15 December 2010
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 185 (12), 7443-7451
- https://doi.org/10.4049/jimmunol.1000446
Abstract
Peripheral blood and tissue eosinophilia is a prominent feature in allergic diseases and helminth infections. In cancer patients, tumor-associated tissue eosinophilia is frequently observed. Tumor-associated tissue eosinophilia can be associated with a favorable prognosis, notably in colorectal carcinoma. However, underlying mechanisms of eosinophil contribution to antitumor responses are poorly understood. We have in this study investigated the direct interactions of human eosinophils with Colo-205, a colorectal carcinoma cell line, and show that eosinophils induce apoptosis and directly kill tumor cells. Using blocking Abs, we found that CD11a/CD18 complex is involved in the tumoricidal activity. Coculture of eosinophils with Colo-205 led to the release of eosinophil cationic protein and eosinophil-derived neurotoxin as well as TNF-α secretion. Moreover, eosinophils expressed granzyme A, which was released upon interaction with Colo-205, whereas cytotoxicity was partially inhibited by FUT-175, an inhibitor of trypsin-like enzymatic activity. Our data present the first demonstration, to our knowledge, that granzyme A is a cytotoxic mediator of the eosinophil protein arsenal, exerting eosinophil tumoricidal activity toward Colo-205, and provide mechanistic evidence for innate responses of eosinophil against tumor cells.Keywords
This publication has 51 references indexed in Scilit:
- TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B CellsBMC Cell Biology, 2010
- A Functional γδTCR/CD3 Complex Distinct from γδT Cells Is Expressed by Human EosinophilsPLOS ONE, 2009
- Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentiallyJournal of Leukocyte Biology, 2008
- The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expressionJournal of Leukocyte Biology, 2008
- Death by a Thousand Cuts: Granzyme Pathways of Programmed Cell DeathAnnual Review of Immunology, 2008
- Expression of granzyme A in human polymorphonuclear neutrophilsImmunology, 2007
- Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host responseJournal of Leukocyte Biology, 2006
- Granzyme A: an additional weapon of human polymorphonuclear neutrophils (PMNs) in innate immunity?Blood, 2004
- Functional significance of the perforin/granzyme cell death pathwayNature Reviews Immunology, 2002
- Crystallographic and functional studies of a modified form of eosinophil-derived neurotoxin (EDN) with novel biological activitiesJournal of Molecular Biology, 2002