title: Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors.
abstract: In this study we have analyzed the interaction between in vitro cultured bone marrow stromal cells (BMSC) and NK cells. Ex vivo-isolated NK cells neoexpressed the activation Ag CD69 and released IFN-gamma and TNF-alpha upon binding with BMSC. Production of these proinflammatory cytokines was dependent on ligation of ICAM1 expressed on BMSC and its receptor LFA1 on NK cells. Furthermore, the NKp30, among natural cytotoxicity receptors, appeared to be primarily involved in triggering NK cells upon interaction with BMSC. Unexpectedly, autologous IL-2-activated NK cells killed BMSC. Again, LFA1/ICAM1 interaction plays a key role in NK/BMSC interaction; this interaction is followed by a strong intracellular calcium increase in NK cells. More importantly, NKG2D/MHC-I-related stress-inducible molecule A and/or NKG2D/UL-16 binding protein 3 engagement is responsible for the delivery of a lethal hit. It appears that HLA-I molecules do not protect BMSC from NK cell-mediated injury. Thus, NK cells, activated upon binding with BMSC, may regulate BMSC survival.
authors.affiliation: Laboratory of Experimental Oncology D, National Cancer Research Institute, Genoa, Italy. alessandro.poggi@istge.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
authors.forename: Claudia
authors.initials: C
authors.lastname: Prevosto
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Massaro
authors.forename: Simone
authors.initials: S
authors.lastname: Negrini
authors.forename: Serena
authors.initials: S
authors.lastname: Urbani
authors.forename: Ivana
authors.initials: I
authors.lastname: Pierri
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Maria Raffaella
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D017154:Stromal Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; C431710:NCR3 protein, human; C423229:ULBP3 protein, human