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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1184-1191. Prepublished online as a Blood First Edition Paper on September 29, 2005; DOI 10.1182/blood-2005-03-1337. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1337v1 107/3/1184    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 Hanaoka, N. Articles by Nakakuma, H. Search for Related Content PubMed PubMed Citation Articles by Hanaoka, N. Articles by Nakakuma, H. Related Collections Immunobiology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP Nobuyoshi Hanaoka, Tatsuya Kawaguchi, Kentaro Horikawa, Shoichi Nagakura, Hiroaki Mitsuya, and Hideki Nakakuma From the Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Division of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; and the Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan. The mechanism by which paroxysmal nocturnal hemoglobinuria (PNH) clones expand is unknown. PNH clones harbor PIGA mutations and do not synthesize glycosylphosphatidylinositol (GPI), resulting in deficiency of GPI-linked membrane proteins. GPI-deficient blood cells often expand in patients with aplastic anemia who sustain immune-mediated marrow injury putatively induced by cytotoxic cells, hence suggesting that the injury allows PNH clones to expand selectively. We previously reported that leukemic K562 cells preferentially survived natural killer (NK) cell-mediated cytotoxicity in vitro when they acquired PIGA mutations. We herein show that the survival is ascribable to the deficiency of stress-inducible GPI-linked membrane proteins ULBP1 and ULBP2, which activate NK and T cells. The ULBPs were detected on GPI-expressing but not on GPI-deficient K562 cells. In the presence of antibodies to either the ULBPs or their receptor NKG2D on NK cells, GPI-expressing cells were as less NK sensitive as GPI-deficient cells. NK cells therefore spared ULBP-deficient cells in vitro. The ULBPs were identified only on GPI-expressing blood cells of a proportion of patients with PNH but none of healthy individuals. Granulocytes of the patients partly underwent killing by autologous cytotoxic cells, implying ULBP-associated blood cell injury. In this setting, the lack of ULBPs may allow immunoselection of PNH clones. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Hanaoka, T. Kawaguchi, K. Horikawa, S. Nagakura, Y. Tsuzuki, Y. Yonemura, and H. Nakakuma ULBP and MICA/B as Novel Indicators for Both Diagnosis of Immune-Mediated Marrow Injury and Favorable Response to Immunosuppressive Therapy in Bone Marrow Failure Syndromes. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 990 - 990. [Abstract] [PDF] N. S. Young, R. T. Calado, and P. Scheinberg Current concepts in the pathophysiology and treatment of aplastic anemia Blood, October 15, 2006; 108(8): 2509 - 2519. [Abstract] [Full Text] [PDF] G. Suck, D. R. Branch, P. Aravena, M. Mathieson, S. Helke, and A. Keating Constitutively polarized granules prime KHYG-1 NK cells Int. Immunol., September 1, 2006; 18(9): 1347 - 1354. [Abstract] [Full Text] [PDF] N. S. Young Pathophysiologic Mechanisms in Acquired Aplastic Anemia Hematology, January 1, 2006; 2006(1): 72 - 77. [Abstract] [Full Text] [PDF]

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