SEARCH:   Advanced

This Article Full Text Full Text (PDF) Erratum (v96,p863) 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 Bang, K. W. A. Articles by Semple, J. W. Search for Related Content PubMed PubMed Citation Articles by Bang, K. W. A. Articles by Semple, J. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 95 No. 5 (March 1), 2000: pp. 1735-1742 Unique processing pathways within recipient antigen-presenting cells determine IgG immunity against donor platelet MHC antigens K. W. Annie Bang, Edwin R. Speck, Victor S. Blanchette, John Freedman, and John W. Semple Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Division of Hematology/Oncology, The Hospital for Sick Children, Departments of Pharmacology, Medicine and Pediatrics, University of Toronto and the Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada. Recipient IgG immunity against leukoreduced donor platelets is dependent on indirect T-cell allorecognition and is suppressed in vivo by inhibitors (aminoguanidine, AMG) of inducible nitric oxide synthase (iNOS). To examine recipient processing pathways of donor platelet antigens, enriched macrophages (antigen-presenting cells [APC]) from BALB/c (H-2d) mice were pulsed with allogeneic C57BL/6 (H-2b) platelets and transfused weekly into naive BALB/c mice. Platelet-pulsed APC stimulated IgG antidonor antibody production in 45% of recipients by the second transfusion and in 100% by the sixth transfusion; this response was enhanced by pulsing in the presence of interferon-. By the sixth transfusion, high-titer IgG1 (mean titer 4990) and IgG2a (1933) isotypes specific for donor major histocompatibility complex (MHC) class I antigens were detected. Platelet pulsing in the presence of AMG or colchicine significantly inhibited the ability of APC to stimulate IgG alloantibodies; only 50% (P < .005) and 20% (P < .0001) of recipients, respectively, produced antibodies by the sixth transfusion. AMG inhibition was reversed by the addition of L-arginine, the substrate for iNOS. In contrast, pulsing in the presence of chloroquine, the proteasome inhibitory peptide MG115, or Brefeldin A enhanced APC immunity (70-100% of recipients antibody positive by the second transfusion [P < .05]); these agents allowed the pulsed APC to stimulate IgG2a but inhibited IgG1 production and this correlated with a reduction in serum interleukin (IL)-4 levels. The results suggest that for donor platelet antigens to stimulate IgG alloantibodies, recipient APC use the essential generation of nitric oxide and a noncytosolic, pH-independent processing pathway, which can be exploited as an effective immunotherapy target to further inhibit alloimmunization against leukoreduced platelets. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Sayeh, K. Sterling, E. Speck, J. Freedman, and J. W. Semple IgG antiplatelet immunity is dependent on an early innate natural killer cell-derived interferon-{gamma} response that is regulated by CD8+ T cells Blood, April 1, 2004; 103(7): 2705 - 2709. [Abstract] [Full Text] [PDF]

	Copyright © 2000 by American Society of Hematology         Online ISSN: 1528-0020