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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3881-3889. Prepublished online as a Blood First Edition Paper on January 23, 2007; DOI 10.1182/blood-2006-08-044669. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-044669v1 109/9/3881    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 Florey, O. J Articles by Haskard, D. O Search for Related Content PubMed PubMed Citation Articles by Florey, O. J Articles by Haskard, D. O Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 31, 2006 Accepted December 1, 2006 Anti-endothelial cell antibodies mediate enhanced leukocyte adhesion to cytokine-activated endothelial cells through a novel mechanism requiring cooperation between FcRIIa and CXCR1/2 Oliver J Florey, Michael Johns, Olubukola O Esho, Justin C Mason, and Dorian O Haskard* BHF Cardiovascular Medicine, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom * Corresponding author; email: d.haskard{at}imperial.ac.uk. Anti-endothelial cell antibodies (AECA) are commonly detectable in diseases associated with vascular injury, including systemic lupus erythematosus (SLE), systemic sclerosis, Takayasu’s arteritis, Wegener’s granulomatosis, Behçet’s syndrome and transplant arteriosclerosis. Here, we explore the hypothesis that these antibodies might augment polymorphonuclear leukocyte (PMN) adhesion to endothelium in inflammation. Initially, we established that a mouse IgG mAb bound to EC significantly increased PMN adhesion to cytokine-stimulated endothelium in an FcRIIa-dependent manner. Neutralizing antibodies, and adenoviral transduction of resting EC, demonstrated that the combination of E-selectin, CXCR1/2 and 2 integrins is both necessary and sufficient for this process. We observed an identical mechanism using AECA IgG isolated directly from patients with SLE. Assembled immune-complexes also enhanced PMN adhesion to endothelium, but, in contrast to adhesion due to AECA, this process did not require CXCR1/2, was not inhibited by pertussis toxin and was FcRIIIb rather than FcRIIa dependent. These data are the first to demonstrate separate non-redundant FcRIIa and FcRIIIb-mediated mechanisms by which EC-bound monomeric IgG and assembled immune-complexes amplify leukocyte adhesion under dynamic conditions. Furthermore, the observation that FcRIIa and CXCR1/2 co-operate to enhance PMN recruitment in the presence of AECA suggests a mechanism whereby AECA may augment tissue injury during inflammatory responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FcRs join in the cascade Francis W. Luscinskas and Tanya Mayadas Blood 2007 109: 3615-3616. [Full Text] [PDF] This article has been cited by other articles: T. N. Mayadas, G. C. Tsokos, and N. Tsuboi Mechanisms of Immune Complex-Mediated Neutrophil Recruitment and Tissue Injury Circulation, November 17, 2009; 120(20): 2012 - 2024. [Full Text] [PDF] O. Florey and D. O. Haskard Sphingosine 1-Phosphate Enhances Fc{gamma} Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions J. Immunol., August 15, 2009; 183(4): 2330 - 2336. [Abstract] [Full Text] [PDF]

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