Lipoxina

Lipoxin A4 Inhibits Porphyromonas gingivalis -Induced Aggregation and Reactive Oxygen Species Production by Modulating Neutrophil-Platelet Interaction and CD11b Expression
Downloaded from http://iai.asm.org/ on May 23, 2012 by UNIVERSIDAD DE CONCEPCION Emma Börgeson, Johanna Lönn, Ida Bergström, Veronika Patcha Brodin, Sofia Ramström, Fariba Nayeri, Eva Särndahl and Torbjörn Bengtsson Infect.Immun. 2011, 79(4):1489. DOI: 10.1128/IAI.00777-10. Published Ahead of Print 24 January 2011.

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http://iai.asm.org/content/suppl/2011/03/09/79.4.1489.DC1.html This article cites 68 articles, 25 of which can be accessed free at:http://iai.asm.org/content/79/4/1489#ref-list-1 Receive: RSS Feeds, eTOCs, free email alerts (when new articles cite this article), more»

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INFECTION AND IMMUNITY, Apr. 2011, p. 1489–1497 0019-9567/11/$12.00doi:10.1128/IAI.00777-10 Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Vol. 79, No. 4

Lipoxin A4 Inhibits Porphyromonas gingivalis-Induced Aggregation and Reactive Oxygen Species Production by Modulating Neutrophil-Platelet Interaction and CD11b Expression †‡
Emma Borgeson,1,2# Johanna Lonn,2,3,4#* Ida Bergstrom,5 Veronika Patcha Brodin,6 ¨ ¨ ¨ Sofia Ramstrom,7 Fariba Nayeri,4Eva Sarndahl,3 and Torbjorn Bengtsson2,3 ¨ ¨ ¨
School of Medicine and Medical Science, University College Dublin Diabetes Research Centre, Conway Institute, University College Dublin, Belfield, Dublin, Ireland1; Division of Drug Research2 and Division of Cardiovascular Medicine,5 Department of Medical and Health Sciences, and Division of Medical Microbiology6 and Division of Clinical Chemistry,7Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden; Division of Clinical Medicine, ¨ ¨ ¨ ¨ School of Health and Medical Sciences, Orebro University, Orebro, Sweden3; and PEAS Institute, Linkoping, Sweden4 ¨
Received 19 July 2010/Returned for modification 20 August 2010/Accepted 23 December 2010

Downloaded from http://iai.asm.org/on May 23, 2012 by UNIVERSIDAD DE CONCEPCION

Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygenspecies (ROS) production and aggregation. Lipoxin A4 (LXA4) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA4 on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROSproduction was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 andupregulates CD11b/ CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA4. Furthermore, we found that LXA4 significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA4 was unable to inhibit either aggregation or ROS production, respectively. In...