title: Adhesion of tumoricidal eosinophils to MCA-38 colon adenocarcinoma cells involves protein tyrosine kinase activation and is diminished by elevated cyclic AMP in the effector cell.
abstract: Although eosinophils have been implicated in immune responses to certain types of tumors, the mechanisms of anti-tumor activity by eosinophils are poorly understood. We show here that mouse eosinophils kill allogeneic MCA-38 colon adenocarcinoma cells in the absence of specific anti-body. Eosinophil adhesion to MCA-38 monolayers occurred within 15 min and plateaued at 90 min. Although mouse eosinophils express alphaL (CD11a), alphaM (CD11b), and alpha4 (CD49d) integrin chains, blocking antibody studies revealed that these molecules are not involved in eosinophil binding to MCA-38 cells. Adhesion was also fibronectin-independent. Binding was inhibited when eosinophils, but not MCA-38 cells, were pretreated with methyl 2,5-dihydroxycinnamate (MDHC), a selective inhibitor of protein tyrosine kinases, or 8-Br-cAMP-Na, a cell-permeable cyclic AMP analogue. Adhesion was unaffected by calphostin C, a specific inhibitor of protein kinase C, and wortmannin, a selective inhibitor of phosphatidylinositol 3-kinases.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.forename: T D
authors.initials: TD
authors.lastname: Lee
authors.forename: D W
authors.initials: DW
authors.lastname: Hoskin
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism*; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D016023:Integrins; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases