2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007111166v1 19/5/973    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 Google Scholar Articles by Nolan, S. L. Articles by Savage, C. O.S. PubMed PubMed Citation Articles by Nolan, S. L. Articles by Savage, C. O.S. Related Collections Related Article

Mechanisms of ANCA-Mediated Leukocyte-Endothelial Cell Interactions In Vivo

Sarah L. Nolan^*, Neena Kalia, Gerard B. Nash, Dia Kamel, Peter Heeringa and Caroline O.S. Savage^*

^* Renal Immunobiology, Centre for Cardiovascular Sciences, and Department of Pathology, Medical School, University of Birmingham, Birmingham, United Kingdom; and Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Centre, Groningen, Netherlands

Correspondence: Prof. Caroline O.S. Savage, Renal Immunobiology, MRC Centre for Immune Regulation, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK. Phone: +44-121-697-8427; Fax: +44-121-414-6794; E-mail: C.O.S.Savage{at}bham.ac.uk

Received for publication November 2, 2007. Accepted for publication January 3, 2008.

Anti-myeloperoxidase (anti-MPO) antibodies have been implicated in the pathogenesis of small-vessel vasculitis, but the molecular mechanisms by which these antibodies contribute to disease are unknown. For determination of how anti-MPO antibodies affect inflammatory cell recruitment in small-vessel vasculitis, intravital microscopy was used to monitor leukocyte behavior in the accessible cremasteric microvessels under various experimental conditions. After local pretreatment of the cremaster muscle with cytokines (TNF-, IL-1β, or keratinocyte-derived chemokine), administration of anti-MPO IgG to wild-type mice reduced leukocyte rolling in favor of augmented adhesion to and transmigration across the endothelium. This led to a decrease in the number of systemic circulating leukocytes and, similar to the early events in the development of vasculitic lesions, an increase in leukocyte recruitment to renal and pulmonary tissue. TNF- led to the greatest recruitment of inflammatory cells, and IL-1β led to the least. When anti-CD18 was co-administered, anti-MPO IgG did not affect leukocyte rolling, adhesion, or transmigration; similarly, anti-MPO IgG did not produce these effects in Fc receptor chain^–/– mice. This study provides direct in vivo evidence of enhanced leukocyte–endothelial cell interactions in the presence of anti-MPO IgG and highlights the critical roles of Fc receptors and β₂ integrins in mediating these interactions. In addition, it suggests that neutrophils primed by cytokines in the presence of anti-MPO IgG can have systemic effects and target specific vascular beds.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2008 19: A7. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673