title: Stimulation of IL-2-activated natural killer cells through the Kp43 surface antigen up-regulates TNF-alpha production involving the LFA-1 integrin.
abstract: We have previously described that a mAb directed against a surface dimer (Kp43) expressed by NK cells was able to regulate cell proliferation, enhance the cytotoxicity of IL-2-activated NK cells, and activate phospholipase D. In this work we have analyzed the ability of the anti-Kp43 mAb to regulate the production of TNF-alpha. Our results show that the stimulation of IL-2-activated NK cells with soluble anti-Kp43 mAb or its F(ab')2 activated the secretion of the cytokine, inasmuch as this effect is associated with the induction of cellular aggregation. The intensity of the Kp43-mediated stimulation varied among different IL-2-activated NK cell samples. Even in those instances where the anti-Kp43 mAb alone could not detectably enhance TNF-alpha production, it displayed a synergistic effect combined to a soluble anti-CD16 mAb, which on its own did not efficiently activate cytokine production. The anti-Kp43 mAb also cooperated with a phorbol ester, although it did not modify the TNF-alpha production triggered by a Ca2+ ionophore. The anti-Kp43-mediated effect, which required the preactivation of cells with IL-2, was inhibited by cycloheximide and actinomycin D and was associated with an increase in the levels of TNF-alpha-specific mRNA. It is noteworthy that the Kp43-mediated production of TNF-alpha was partially inhibited by anti-CD18, anti-CD11a and anti-ICAM-1 mAb that blocked LFA-1-dependent cellular interactions, which impaired NK cell aggregation and, moreover, was dependent on the presence of extracellular Mg2+, thus suggesting that the leukocyte integrin is involved in the activation process triggered through Kp43.
authors.affiliation: Sección de Inmunología, Hospital de la Princesa, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Aramburu
authors.forename: M A
authors.initials: MA
authors.lastname: Balboa
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.forename: I
authors.initials: I
authors.lastname: Melero
authors.forename: M
authors.initials: M
authors.lastname: Alonso
authors.forename: J L
authors.initials: JL
authors.lastname: Alonso
authors.forename: M
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate