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.2006090973v1 18/4/1112    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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Williams, J. M. Articles by Wakelam, M. J.O. Search for Related Content PubMed PubMed Citation Articles by Williams, J. M. Articles by Wakelam, M. J.O.

Antineutrophil Cytoplasm Antibody–Stimulated Neutrophil Adhesion Depends on Diacylglycerol Kinase–Catalyzed Phosphatidic Acid Formation

Julie M. Williams^*, Trevor R. Pettitt, Wendy Powell^*, Joseph Grove^*, Caroline O.S. Savage^* and Michael J.O. Wakelam

^* Renal Immunobiology and Medical Research Council Centre for Immune Regulation and CR-UK Institute for Cancer Studies, Birmingham University, Birmingham, United Kingdom

Address correspondence to: Dr. Michael J.O. Wakelam, CR-UK Institute for Cancer Studies, Birmingham University, Birmingham B15 2TT, UK. Phone: +44-121-4143293; Fax: +44-121-4144486; E-mail: m.j.o.wakelam{at}bham.ac.uk

Received for publication September 7, 2006. Accepted for publication January 31, 2007.

Patients with certain forms of systematic vasculitis, such as Wegener's granulomatosis, have circulating antineutrophil cytoplasmic antibodies (ANCA). These inappropriately stimulate circulating neutrophils adhere to and thereby obstruct small vessels. This, together with ANCA-induced degranulation and an oxidative burst, leads to local tissue damage. The signaling pathways that are activated by ANCA IgG are distinct from those that are involved in normal neutrophil activation. This study shows that diacylglycerol kinase is selectively activated by ANCA and that the generated phosphatidic acid is responsible for promoting neutrophil adhesion, in part through integrin activation. The data presented point to diacylglycerol kinase as a novel but selective target for the development of drugs to treat this potentially fatal disorder.

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