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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 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 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 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 Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Cell Adhesion and Motility Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antineutrophil cytoplasm antibodies directed against myeloperoxidase augment leukocyte-microvascular interactions in vivo Mark A. Little, C. Lucy Smyth, Rashmi Yadav, Lyn Ambrose, H. Terence Cook, Sussan Nourshargh, and Charles D. Pusey From The Eric Bywaters Centre for Vascular Inflammation, London, United Kingdom; the Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom; and the Department of Histopathology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom. Systemic small vessel vasculitis is associated with antineutrophil cytoplasm antibodies (ANCAs). While there is mounting in vitro evidence to suggest that ANCAs 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 immunization with human myeloperoxidase (MPO), was used to analyze directly the potential effect of ANCAs on leukocyte-venular wall interactions in vivo as observed by intravital microscopy. These rats developed anti-MPO antibodies directed against rat leukocytes, showed pathologic evidence of small vessel vasculitis, and had enhanced leukocyte adhesion and transmigration in response to the chemokine Gro (CXCL1 [CXC ligand 1]). 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 hemorrhage, in response to CXCL1. This study provides the first direct in vivo evidence for the ability of ANCAs to enhance leukocyteendothelial interactions and cause microvascular hemorrhage, thereby providing a mechanism by which ANCAs could exert pathogenic effects in systemic vasculitis. (Blood. 2005;106:2050-2058) 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: S. L. Nolan, N. Kalia, G. B. Nash, D. Kamel, P. Heeringa, and C. O.S. Savage Mechanisms of ANCA-Mediated Leukocyte-Endothelial Cell Interactions In Vivo J. Am. Soc. Nephrol., May 1, 2008; 19(5): 973 - 984. [Abstract] [Full Text] [PDF] R. A.F. de Lind van Wijngaarden, L. van Rijn, E. C. Hagen, R. A. Watts, G. Gregorini, J. W. C. Tervaert, A. D. Mahr, J. L. Niles, E. de Heer, J. A. Bruijn, et al. Hypotheses on the Etiology of Antineutrophil Cytoplasmic Autoantibody Associated Vasculitis: The Cause Is Hidden, but the Result Is Known Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 237 - 252. [Abstract] [Full Text] [PDF] Y. M van der Geld, T. Hellmark, D. Selga, P. Heeringa, M. G Huitema, P. C Limburg, and C. G M Kallenberg Rats and mice immunised with chimeric human/mouse proteinase 3 produce autoantibodies to mouse Pr3 and rat granulocytes Ann Rheum Dis, December 1, 2007; 66(12): 1679 - 1682. [Abstract] [Full Text] [PDF] S. Lionaki and R. J. Falk Removing Antibody and Preserving Glomeruli in ANCA Small-Vessel Vasculitis J. Am. Soc. Nephrol., July 1, 2007; 18(7): 1987 - 1989. [Full Text] [PDF] D. R.W. Jayne, G. Gaskin, N. Rasmussen, D. Abramowicz, F. Ferrario, L. Guillevin, E. Mirapeix, C. O.S. Savage, R. A. Sinico, C. A. Stegeman, et al. Randomized Trial of Plasma Exchange or High-Dosage Methylprednisolone as Adjunctive Therapy for Severe Renal Vasculitis J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2180 - 2188. [Abstract] [Full Text] [PDF] R. Colman, A. Hussain, M. Goodall, S. P Young, T. Pankhurst, X. Lu, R. Jefferis, C. O S Savage, and J. M Williams Chimeric antibodies to proteinase 3 of IgG1 and IgG3 subclasses induce different magnitudes of functional responses in neutrophils Ann Rheum Dis, May 1, 2007; 66(5): 676 - 682. [Abstract] [Full Text] [PDF] H. Xiao, A. Schreiber, P. Heeringa, R. J. Falk, and J. C. Jennette Alternative Complement Pathway in the Pathogenesis of Disease Mediated by Anti-Neutrophil Cytoplasmic Autoantibodies Am. J. Pathol., January 1, 2007; 170(1): 52 - 64. [Abstract] [Full Text] [PDF] A. Schreiber, H. Xiao, R. J. Falk, and J. C. Jennette Bone Marrow-Derived Cells Are Sufficient and Necessary Targets to Mediate Glomerulonephritis and Vasculitis Induced by Anti-Myeloperoxidase Antibodies J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3355 - 3364. [Abstract] [Full Text] [PDF] D. Huugen, J. W. Cohen Tervaert, and P. Heeringa TNF-{alpha} Bioactivity-Inhibiting Therapy in ANCA-Associated Vasculitis: Clinical and Experimental Considerations Clin. J. Am. Soc. Nephrol., September 1, 2006; 1(5): 1100 - 1107. [Abstract] [Full Text] [PDF] A.-J. Ruth, A. R. Kitching, R. Y.Q. Kwan, D. Odobasic, J. D.K. Ooi, J. R. Timoshanko, M. J. Hickey, and S. R. Holdsworth Anti-Neutrophil Cytoplasmic Antibodies and Effector CD4+ Cells Play Nonredundant Roles in Anti-Myeloperoxidase Crescentic Glomerulonephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1940 - 1949. [Abstract] [Full Text] [PDF] M. D. Morgan, L. Harper, J. Williams, and C. Savage Anti-Neutrophil Cytoplasm-Associated Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1224 - 1234. [Abstract] [Full Text] [PDF] J. C. Jennette, H. Xiao, and R. J. Falk Pathogenesis of Vascular Inflammation by Anti-Neutrophil Cytoplasmic Antibodies J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1235 - 1242. [Abstract] [Full Text] [PDF] M. Feldmann and C. D. Pusey Is There a Role for TNF-{alpha} in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1243 - 1252. [Abstract] [Full Text] [PDF] C. D. Pusey The Continuing Challenge of Anti-Neutrophil Cytoplasm Antibody-Associated Systemic Vasculitis and Glomerulonephritis J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1221 - 1223. [Full Text] [PDF] M. A. Little, G. Bhangal, C. L. Smyth, M. T. Nakada, H. T. Cook, S. Nourshargh, and C. D. Pusey Therapeutic Effect of Anti-TNF-{alpha} Antibodies in an Experimental Model of Anti-Neutrophil Cytoplasm Antibody-Associated Systemic Vasculitis J. Am. Soc. Nephrol., January 1, 2006; 17(1): 160 - 169. [Abstract] [Full Text] [PDF]

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