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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6485-6494. Prepublished online as a Blood First Edition Paper on April 21, 2009; DOI 10.1182/blood-2008-12-192617. This Article Full Text (PDF) All Versions of this Article: blood-2008-12-192617v1 113/25/6485    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuligowski, M. P. Articles by Hickey, M. J. Search for Related Content PubMed PubMed Citation Articles by Kuligowski, M. P. Articles by Hickey, M. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 4, 2008 Accepted April 16, 2009 Anti-myeloperoxidase antibodies rapidly induce 4 integrin-dependent glomerular neutrophil adhesion Michael P. Kuligowski, Rain Y.Q. Kwan, Cecilia Lo, Cyndi Wong, Will G. James, Dorothee Bourges, Joshua D. Ooi, Latasha D. Abeynaike, Pam Hall, A. Richard Kitching, and Michael J. Hickey* Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia Department of Nephrology and Pediatric Nephrology, Monash Medical Centre, Clayton, Victoria, Australia * Corresponding author; email: michael.hickey{at}med.monash.edu.au. Patients with anti-neutrophil cytoplasmic antibodies (ANCA) frequently develop severe vasculitis and glomerulonephritis. Despite the fact that ANCAs, particularly anti-myeloperoxidase (anti-MPO), have been shown to promote leukocyte adhesion in postcapillary venules, their ability to promote adhesion in the glomerular vasculature is less clear. We used intravital microscopy to examine glomerular leukocyte adhesion induced by anti-MPO. In mice pretreated with LPS, 50 µg of anti-MPO induced LFA-1-dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, > 80% of circulating neutrophils bound anti-MPO within 5 min of intravenous administration. However, even in the absence of LPS, > 40% of circulating neutrophils bound anti-MPO in vivo, a response not seen in MPO-/- mice. In addition, a higher dose of anti-MPO (200 µg) induced robust glomerular leukocyte adhesion in the absence of LPS. The latter response was 2-integrin-independent, instead requiring the 4-integrin, which was upregulated on neutrophils in response to anti-MPO. These data indicate that anti-MPO antibodies bind to circulating neutrophils, and can induce glomerular leukocyte adhesion via multiple pathways. Lower doses only induce adhesion after an infection-related stimulus, whereas higher doses are capable of inducing responses in the absence of an additional inflammatory stimulus, via alternative adhesion mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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