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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 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 Citation Map 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 Immunobiology Phagocytes Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Reciprocal regulation of human natural killer cells and macrophages associated with distinct immune synapses Shlomo Nedvetzki1, Stefanie Sowinski1, Robert A. Eagle2, James Harris3, Frédéric Vély4, Daniela Pende5, John Trowsdale2, Eric Vivier4, Siamon Gordon3, and Daniel M. Davis1 1 Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, United Kingdom; 2 Department of Pathology, Cambridge Institute for Medical Research, Addenbrookes Hospital, United Kingdom; 3 Sir William Dunn School of Pathology, University of Oxford, United Kingdom; 4 Centre d'Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique (CNRS)–Institut National de la Santé et de la Recherche Médicale (INSERM)–Université de la Méditerranée, Campus de Luminy, Marseille, France; 5 Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy Natural killer (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 and 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 major histocompatibility complex (MHC)–like ligands on macrophages: high doses of LPS induced transcription and surface expression of ULBP1, ULBP2, and ULBP3 and surface expression of constitutively transcribed MICA. Thus, these data suggest a new function for NK cell cytotoxicity in eliminating overstimulated macrophages. Additionally, these interactions define, for the first time, 2 distinct activating NK cell synapses: lytic and nonlytic. 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 NK cell 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. DeMatteo The Lytic Potential of Human Liver NK Cells Is Restricted by Their Limited Expression of Inhibitory Killer Ig-Like Receptors J. Immunol., August 1, 2009; 183(3): 1789 - 1796. [Abstract] [Full Text] [PDF] S. D. Smith, C. E. Dunk, J. D. Aplin, L. K. Harris, and R. L. 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