title: IL-18 Is Involved in Eosinophil-Mediated Tumoricidal Activity against a Colon Carcinoma Cell Line by Upregulating LFA-1 and ICAM-1.
abstract: Eosinophils are multifunctional leukocytes that are involved in innate and adaptive immune responses through the expression of various receptors and mediators. Previously, we showed that human eosinophils and T cells shared cytotoxic activities against tumor cells that involved the γ-δ TCR and cell-cell contact. In this study, we investigated the molecules involved in eosinophil-tumor cell interactions. Given the role of IL-18 in cell adhesion and in protecting against colon cancer, we evaluated its role in eosinophil-mediated cytotoxicity against Colo-205, a human colon carcinoma cell line. We found that human eosinophils exerted dose- and time-dependent tumoricidal activity against Colo-205 cells. Neutralization of IL-18 significantly reduced eosinophil-mediated Colo-205 apoptosis and inhibited cell-cell adhesion. Moreover, addition of rIL-18 led to upregulation of CD11a and ICAM-1 adhesion molecules, which were involved in the contact between eosinophils and Colo-205 cells. Our results indicated that IL-18 was involved in the eosinophil-mediated death of Colo-205 by facilitating contact between effector and target cells. These data underscored the involvement of an additional mediator in eosinophil-mediated antitumor cytotoxicity. Our findings support existing evidence that eosinophils could play a beneficial role in the context of colon cancer.
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France; solene.gatault@hotmail.fr.
authors.forename: Solène
authors.initials: S
authors.lastname: Gatault
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Delbeke
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France;
authors.forename: Virginie
authors.initials: V
authors.lastname: Driss
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France;
authors.forename: Aurore
authors.initials: A
authors.lastname: Sarazin
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France;
authors.forename: Arnaud
authors.initials: A
authors.lastname: Dendooven
authors.affiliation: Service de Médecine Interne, Hôpital Foch, Université Versailles Saint Quentin en Yvelines, 92150 Suresnes, France; Réseau Eosinophile Français, EA2686, Université de Lille, 59045 Lille, France; and.
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Kahn
authors.affiliation: Réseau Eosinophile Français, EA2686, Université de Lille, 59045 Lille, France; and Institut d'Immunologie, Service de Médecine Interne, Unité d'Immunologie Clinique, CHRU de Lille, 59045 Lille, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lefèvre
authors.affiliation: LIRIC-Unité Mixte de Recherche 995 INSERM, Université de Lille 2, CHRU de Lille, 59045 Lille, France;
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D040881:CD11a Antigen / Q000276:immunology / Q000378:metabolism; D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
chemical_list: D040881:CD11a Antigen; D020382:Interleukin-18; D016169:Lymphocyte Function-Associated Antigen-1; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1