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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2050-2058. Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2005-03-0921. This Article Full Text (PDF) Supplemental Video All Versions of this Article: 2005-03-0921v1 106/6/2050    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 Little, M. A Articles by Pusey, C. D Search for Related Content PubMed PubMed Citation Articles by Little, M. A Articles by Pusey, C. D Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 7, 2005 Accepted May 18, 2005 Anti-neutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo Mark A Little, C L Smyth, Rashmi Yadav, Lyn Ambrose, H T Cook, Sussan Nourshargh, and Charles D Pusey* The Eric Bywaters Centre for Vascular Inflammation, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom; Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom The Eric Bywaters Centre for Vascular Inflammation, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom Department of Histopathology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom * Corresponding author; email: c.pusey{at}imperial.ac.uk. Systemic small vessel vasculitis is associated with anti-neutrophil cytoplasm antibodies (ANCA). Whilst there is mounting in vitro evidence to suggest that ANCA are capable of enhancing leukocyte-endothelial interactions, no in vivo evidence for this has been provided. In this study a novel rat model of ANCA-associated experimental autoimmune vasculitis (EAV), induced by immunisation with human MPO, was used to analyse directly the potential effect of ANCA on leukocyte-venular wall interactions in vivo as observed by intravital microscopy. These rats developed anti-MPO antibodies directed against rat leukocytes, showed pathological evidence of small vessel vasculitis, and had enhanced leukocyte adhesion and transmigration in response to the chemokine Gro (CXCL1). Passive transfer of immunoglobulin from rats with EAV to naive rats conferred enhanced adhesion and transmigration responses in the recipients. Furthermore, rats with EAV and recipients of ANCA-positive immunoglobulin developed extensive microvascular injury, as manifested by mesenteric haemorrhage, in response to CXCL1. This study provides the first direct in vivo evidence for the ability of ANCA to enhance leukocyte-endothelial interactions and cause microvascular haemorrhage, thereby providing a mechanism by which ANCA could exert pathogenic effects in systemic vasculitis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Watching ANCAs work Ingeborg M. Bajema Blood 2005 106: 1889-1890. [Full Text] [PDF] This article has been cited by other articles: M. Chen and C. G. M. Kallenberg Novel territory for neutrophils in the pathogenesis of ANCA-associated vasculitides Nephrol. Dial. Transplant., December 1, 2009; 24(12): 3618 - 3620. [Full Text] [PDF] J. A. Gomez-Puerta and X. 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