Induction of sensitivity to NK-mediated cytotoxicity by TNF-alpha treatment: possible role of ICAM-3 and CD44.
SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low level of ICAM-1. Pre-treatment of SR-91 cells with TNF-alpha or IFN-gamma, increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human NK cell line NK-92. However, only TNF-alpha-treated SR-91 cells became sensitive to killing by NK-92 cells. The increased binding induced by both cytokines and the TNF-alpha-induced sensitivity of SR-91 cells to NK-92 cell killing were abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3 (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells is essential for effector-target cell binding (which is a prerequisite for subsequent target cell lysis), but is insufficient to render the SR-91 cells sensitive to killing by NK-92 cells. TNF-alpha, but not IFN-gamma also induced the activation of LFA-1, CD44 and beta1 integrins on SR-91 cells. Based on these observations we propose that the differential effect of TNF-alpha and IFN-gamma could be related to the activation of certain adhesion molecules on the surface of SR-91 cells by TNF-alpha that, upon interaction with their counter-receptors on NK-92 cells, lead to the activation of the NK-92 cells.
BC Cancer Research Centre, Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
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Maki
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Krystal
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Dougherty
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Takei
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Klingemann
D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation; D002051:Burkitt Lymphoma; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D053938:DNA Fragmentation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; C483616:ICAM3 protein, human; D014409:Tumor Necrosis Factor-alpha