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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3776-3785. Prepublished online as a Blood First Edition Paper on January 11, 2007; DOI 10.1182/blood-2006-10-052977. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2006-10-052977v1 109/9/3776    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nedvetzki, S. Articles by Davis, D. M Search for Related Content PubMed PubMed Citation Articles by Nedvetzki, S. Articles by Davis, D. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 19, 2006 Accepted December 26, 2006 Reciprocal regulation of natural killer cells and macrophages associated with distinct immune synapses Shlomo Nedvetzki, Stefanie Sowinski, Robert A Eagle, James Harris, Frederic Vely, Daniela Pende, John Trowsdale, Eric Vivier, Siamon Gordon, and Daniel M Davis* Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, London, United Kingdom Department of Pathology, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge, United Kingdom Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Universite de la Mediterranee, Marseille, France Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy * Corresponding author; email: d.davis{at}imperial.ac.uk. NK cells directly lyse tumor or viral-infected cells but also, an important role for NK cell cytotoxicity in regulating the extent of immune responses is emerging. Here, we show that autologous human macrophages activated NK cell proliferation, cytokine secretion, increased expression of activating receptors and primed NK cell cytotoxicity against susceptible target cells. Ligation of NK cell 2B4, and not NKp30 known to be important for DC-mediated NK cell activation, is critical for this macrophage-mediated NK cell activation. Reciprocally however, NK cells regulated macrophage activity by directly killing macrophages stimulated by high doses of LPS. Cytolysis was triggered by NKG2D recognition of stress-inducible class I MHC-like ligands: High doses of LPS induced transcription and surface expression of ULBP1, 2 and 3, and surface expression of constitutively transcribed MICA. Thus, these data suggest a new function for NK cell cytotoxicity in eliminating over-stimulated macrophages. Additionally, these interactions define, for the first time, two distinct activating NK cell synapses; lytic and non-lytic. Triggering NK cell proliferation and cytokine secretion, but not cytolysis, specifically associated with synaptic accumulation of macrophage f-actin and NK cell 2B4, while macrophages were killed when NK cell f-actin and macrophage ICAM-1 accumulated around a central cluster of NKG2D/DAP10. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Control LPS or get killed Noam Stern-Ginossar and Ofer Mandelboim Blood 2007 109: 3614-3615. [Full Text] [PDF] This article has been cited by other articles: B. M. Burt, G. Plitas, Z. Zhao, Z. M. Bamboat, H. M. Nguyen, B. Dupont, and R. P. 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