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Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-04-1029. This Article Full Text (PDF) All Versions of this Article: 2003-04-1029v1 102/8/2862    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 Coopamah, M. D Articles by Semple, J. W Search for Related Content PubMed PubMed Citation Articles by Coopamah, M. D Articles by Semple, J. W Social Bookmarking                   What's this? Submitted April 4, 2003 Accepted May 28, 2003 Anti-D (WinRhoSDFTM) initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin 1 receptor antagonist Malini D Coopamah, John Freedman, and John W Semple* Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; Research and Development, Canadian Blood Services, Toronto, Ontario, Canada; Toronto Platelet Immunobiology Group, Toronto, Ontario, Canada Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Research and Development, Canadian Blood Services, Toronto, Ontario, Canada * Corresponding author; email: semplej{at}smh.toronto.on.ca. Previous results have demonstrated that anti-D therapy in children with chronic AITP induced a significant increase in several pro- and anti-inflammatory plasma cytokines within 2 hours of administration. To investigate the biological basis of these early in vivo responses, we developed a flow cytometric assay to measure Fc-dependent responses of human peripheral leukocytes with fluorescently labelled and anti-D-opsonized red blood cells (RBC). When anti-D-opsonized RBC were incubated with peripheral blood leukocytes, the earliest detectible event observed was a significant oxidative burst in both monocytes (p<0.05) and granulocytes (p<0.0001) characterized by the production of hydrogen peroxide (H2O2), peroxynitrite (ONOO-), superoxide (O2-.) and hydroxyl (OH.) by 10 minutes which declined by 1 hour. By 2 hours, the opsonized RBC were phagocytosed, particularly by granulocytes (p<0.001) but the phagocytosis subsequently declined by 6 hours incubation. The decline in phagocytosis was correlated with a significant production of IL1 receptor antagonist (IL1ra) by both monocytes (p=0.036) and granulocytes (p=0.0002) within 4 hours. None of these events occurred if the RBC were coated with anti-D F(ab)'2 fragments. When recombinant IL1ra was titrated into the assay, phagocytosis of the opsonized RBC was significantly inhibited (p=0.002). Taken together, these results suggest that at least one mechanism of action of anti-D is via the production of the anti-inflammatory cytokine IL1ra which can negatively regulate the ability of leukocytes to phagocytose opsonized cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Bruhns, B. Iannascoli, P. England, D. A. Mancardi, N. Fernandez, S. Jorieux, and M. Daeron Specificity and affinity of human Fc{gamma} receptors and their polymorphic variants for human IgG subclasses Blood, April 16, 2009; 113(16): 3716 - 3725. [Abstract] [Full Text] [PDF] I. Ikonomidis, J. P. Lekakis, M. Nikolaou, I. Paraskevaidis, I. Andreadou, T. Kaplanoglou, P. Katsimbri, G. Skarantavos, P. N. Soucacos, and D. 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