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Infection and Immunity, October 2006, p. 5687-5692, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.01940-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Induction of Neutrophil Chemotaxis by the Quorum-Sensing Molecule N-(3-Oxododecanoyl)-L-Homoserine Lactone

Sabine Zimmermann,1 Christof Wagner,1,2 Wencke Müller,1 Gerald Brenner-Weiss,3 Friederike Hug,1 Birgit Prior,1 Ursula Obst,3 and Gertrud Maria Hänsch1*

Institut für Immunologie der Universität Heidelberg, Heidelberg, Germany,1 Klinik für Unfall- und Wiederherstellungschirurgie, Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Ludwigshafen, Germany,2 Institut für Technische Chemie, Forschungszentrum Karlsruhe, Karlsruhe, Germany3

Received 29 November 2005/ Returned for modification 26 March 2006/ Accepted 3 July 2006

Acyl homoserine lactones are synthesized by Pseudomonas aeruginosa as signaling molecules which control production of virulence factors and biofilm formation in a paracrine manner. We found that N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL), but not its 3-deoxo isomer or acyl-homoserine lactones with shorter fatty acids, induced the directed migration (chemotaxis) of human polymorphonuclear neutrophils (PMN) in vitro. By use of selective inhibitors a signaling pathway, comprising phosphotyrosine kinases, phospholipase C, protein kinase C, and mitogen-activated protein kinase C, could be delineated. In contrast to the well-studied chemokines complement C5a and interleukin 8, the chemotaxis did not depend on pertussis toxin-sensitive G proteins, indicating that 3OC12-HSL uses another signaling pathway. Strong evidence for the presence of a receptor for 3OC12-HSL on PMN was derived from uptake studies; by use of radiolabeled 3OC12-HSL, specific and saturable binding to PMN was seen. Taken together, our data provide evidence that PMN recognize and migrate toward a source of 3OC12-HSL (that is, to the site of a developing biofilm). We propose that this early attraction of PMN could contribute to prevention of biofilm formation.

* Corresponding author. Mailing address: Institut für Immunologie der Universität Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Phone: 49-6221-564071. Fax: 49-6221-565536. E-mail: n50{at}ix.urz.uni-heidelberg.de.

Editor: J. F. Urban, Jr.

Infection and Immunity, October 2006, p. 5687-5692, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.01940-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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