Induction of neutrophil chemotaxis by the quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone.
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.
Zimmermann
Sabine
S
Institut für Immunologie der Universität Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Wagner
Christof
C
Müller
Wencke
W
Brenner-Weiss
Gerald
G
Hug
Friederike
F
Prior
Birgit
B
Obst
Ursula
U
Hänsch
Gertrud Maria
GM
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development; D002634:Chemotaxis, Leukocyte; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction
C109860:N-(3-oxododecanoyl)homoserine lactone; C088386:homoserine lactone; D006714:Homoserine; D015107:4-Butyrolactone