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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4306-4312. Prepublished online as a Blood First Edition Paper on January 25, 2007; DOI 10.1182/blood-2006-09-047159. This Article Full Text (PDF) All Versions of this Article: blood-2006-09-047159v1 109/10/4306    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 Gazit, R. Articles by Mandelboim, O. Search for Related Content PubMed PubMed Citation Articles by Gazit, R. Articles by Mandelboim, O. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 13, 2006 Accepted January 17, 2007 NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome Roi Gazit, Memet Aker, Moran Elboim, Hagit Achdout, Gil Katz, Dana Gila Wolf, Shulamit Katzav, and Ofer Mandelboim* Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, Jerusalem, Israel Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel Clinical Virology Unit, Dept of Clinical Microbiology & Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel The Hubert H. Humphrey Center for Experimental Medicine, and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel * Corresponding author; email: oferman{at}md2.huji.ac.il. Griscelli Syndrome (GS) type 2 is an autosomal recessive disorder represented by pigment dilution and impaired CTL activity. NK activity has been scarcely investigated in GS patients. Here we describe a new patient, possessing a hemophagocytic syndrome with a homozygous Q118X nonsense RAB27A mutation. SSP-PCR was developed based on this mutation and is currently used in prenatal genetic analysis. As expected, CTLs in the patient are not functional and NK cytotoxicity against K562 or 721.221 cells is diminished. Surprisingly however, we demonstrate that CD16-mediated killing is intact in this patient and is therefore RAB27A-independent, whereas NKp30-mediated killing is impaired and is therefore RAB27A-dependent. We further analyzed the signaling pathways of these two receptors and demonstrated phosphorylation of Vav1 after CD16 activation, but not after NKp30 engagement. Thus, we identify a novel homozygous mutation in the RAB27A gene of a new GS patient, observe for the first time that some activating NK receptors function in GS patients and demonstrate a functional dichotomy in the killing mediated by these human NK activating receptors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. M. Wood, M. Meeths, S. C. C. Chiang, A. G. Bechensteen, J. J. Boelens, C. Heilmann, H. Horiuchi, S. Rosthoj, O. Rutynowska, J. Winiarski, et al. Different NK cell-activating receptors preferentially recruit Rab27a or Munc13-4 to perforin-containing granules for cytotoxicity Blood, November 5, 2009; 114(19): 4117 - 4127. [Abstract] [Full Text] [PDF] J. Pachlopnik Schmid, D. Moshous, N. Boddaert, B. Neven, L. Dal Cortivo, M. Tardieu, M. Cavazzana-Calvo, S. Blanche, G. de Saint Basile, and A. Fischer Hematopoietic stem cell transplantation in Griscelli syndrome type 2: a single-center report on 10 patients Blood, July 2, 2009; 114(1): 211 - 218. [Abstract] [Full Text] [PDF]

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