title: The bacterial quorum-sensing molecule, N-3-oxo-dodecanoyl-L-homoserine lactone, inhibits mediator release and chemotaxis of murine mast cells.
abstract: OBJECTIVE
  Bacterial colonization relies on communication between bacteria via so-called "quorum-sensing molecules", which include the acyl-homoserine lactone group. Certain acyl-homoserine lactones can modulate mammalian cell function and are thought to contribute to bacterial pathogenicity. Given the role of mast cells in host defense, we investigated the ability of acyl-homoserine lactones to modulate mast cell function.
  
  
  METHODS
  We utilized murine primary mast cell cultures to assess the effect of acyl-homoserine lactones on degranulation and cytokine release in response to different stimuli. We also assessed cell migration in response to chemoattractants. The effect of acyl-homoserine lactones in vivo was tested using a passive cutaneous anaphylaxis model.
  
  
  RESULTS
  Two of the tested quorum-sensing molecules, N-3-oxo-dodecanoyl-L-homoserine lactone and N-Dodecanoyl-L-homoserine lactone, inhibited IgE dependent and independent degranulation and mediator release from primary mast cells. Further testing of N-3-oxo-dodecanoyl-L-homoserine lactone, the most potent inhibitor and a product of Pseudomonas aeruginosa, revealed that it also attenuated chemotaxis and LPS induced cytokine production. In vivo, N-3-oxo-dodecanoyl-L-homoserine lactone inhibited the passive cutaneous anaphylaxis response in mice.
  
  
  CONCLUSIONS
  The ability of N-3-oxo-dodecanoyl-L-homoserine lactone to stabilize mast cells may contribute to the pathogenicity of P. aeruginosa but could potentially be exploited therapeutically in allergic disease.
authors.affiliation: Department of Medicine, Firestone Institute for Respiratory Research and Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Khambati
authors.affiliation: Department of Medicine, Firestone Institute for Respiratory Research and Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Sangsu
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Medicine, Firestone Institute for Respiratory Research and Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Pijnenburg
authors.affiliation: Department of Medicine, Firestone Institute for Respiratory Research and Brain-Body Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Hannah
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Medicine, Firestone Institute for Respiratory Research and Brain-Body Institute, McMaster University, Hamilton, ON, Canada. forsytp@mcmaster.ca.|Department of Medicine, St. Joseph's Healthcare, McMaster University, 50 Charlton Avenue East, T3302, Hamilton, ON, L8N 4A6, Canada. forsytp@mcmaster.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011550:Pseudomonas aeruginosa; D053038:Quorum Sensing; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; C109860:N-(3-oxododecanoyl)homoserine lactone; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D006714:Homoserine; D015107:4-Butyrolactone
keywords: Chemotaxis; Cytokine; Degranulation; Mast cell; Quorum-sensing