Skip to main content

Advertisement

Log in

Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells

  • Original Investigation
  • Published:
Medical Microbiology and Immunology Aims and scope Submit manuscript

Abstract

Quorum sensing system is a cell-to-cell communication system that plays a pivotal role in virulence expression in bacteria. Recent advances have demonstrated that the Pseudomonas aeruginosa quorum sensing molecule, N-3-oxododecanoyl homoserine lactone (3OC12-HSL), exerts effects on mammalian cells and modulates host immune response. Mast cells (MCs) are strategically located in the tissues that are constantly exposed to external stimulus. Therefore, it is very much possible that 3OC12-HSL may interact with MCs. Little is known, however, about specific effects of 3OC12-HSL on MCs. To address this, we investigated the influence of 3OC12-HSL on cell viability, apoptosis, intracellular calcium and cytokine release in MCs. We found that at high concentrations (100 μM), 3OC12-HSL inhibited proliferation and induced apoptosis in P815. The 3OC12-HSL treatment significantly increased intracellular calcium release in both P815 and HMC-1. We also observed that 3OC12-HSL-induced histamine release and degranulation in HMC-1 cells. Furthermore, 3OC12-HSL-induced IL-6 production at lower concentrations (6.25–12.5 μM) but steadily reduced IL-6 production at high concentration (50–100 μM). These data demonstrate that P. aeruginosa 3OC12-HSL affects MCs function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. de Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immun 68:4839–4849. doi:10.1128/IAI.68.9.4839-4849.2000

    Article  PubMed  Google Scholar 

  2. Fuqua C, Parsek MR, Greenberg EP (2001) Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu Rev Genet 35:439–468. doi:10.1146/annurev.genet.35.102401.090913

    Article  PubMed  CAS  Google Scholar 

  3. Smith RS, Harris SG, Phipps R et al (2002) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl) homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 184:1132–1139. doi:10.1128/jb.184.4.1132-1139.2002

    Article  PubMed  CAS  Google Scholar 

  4. Davies DG, Parsek MR, Pearson JP et al (1998) The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280:295–298. doi:10.1126/science.280.5361.295

    Article  PubMed  CAS  Google Scholar 

  5. Hentzer M, Wu H, Andersen JB et al (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815. doi:10.1093/emboj/cdg366

    Article  PubMed  CAS  Google Scholar 

  6. Shiner EK, Rumbaugh KP, Williams SC (2005) Inter-kingdom signaling: deciphering the language of acyl homoserine lactones. FEMS Microbiol Rev 29:935–947. doi:10.1016/j.femsre.2005.03.001

    Article  PubMed  CAS  Google Scholar 

  7. Hughes DT, Sperandio V (2008) Inter-kingdom signalling: communication between bacteria and their hosts. Nat Rev Microbiol 6:111–120. doi:10.1038/nrmicro1836

    Article  PubMed  CAS  Google Scholar 

  8. Kravchenko VV, Kaufmann GF, Mathison JC et al (2008) Modulation of gene expression via disruption of NF-kappaB signaling by a bacterial small molecule. Science 321:259–263. doi:10.1126/science.1156499

    Article  PubMed  CAS  Google Scholar 

  9. Bradding P, Walls AF, Holgate ST (2006) The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol 117:1277–1284. doi:10.1016/j.jaci.2006.02.039

    Article  PubMed  CAS  Google Scholar 

  10. Bischoff SC (2007) Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7:93–104. doi:10.1038/nri2018

    Article  PubMed  CAS  Google Scholar 

  11. Metz M, Maurer M (2007) Mast cells—key effector cells in immune responses. Trends Immunol 28:234–241. doi:10.1016/j.it.2007.03.003

    Article  PubMed  CAS  Google Scholar 

  12. Siebenhaar F, Syska W, Weller K et al (2007) Control of Pseudomonas aeruginosa skin infections in mice is mast cell-dependent. Am J Pathol 170:1910–1916. doi:10.2353/ajpath.2007.060770

    Article  PubMed  CAS  Google Scholar 

  13. Song Z, Johansen HK, Faber V et al (1997) Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats. Antimicrob Agents Chemother 41:961–964

    PubMed  CAS  Google Scholar 

  14. Henderson WR Jr, Chi EY (1992) Degranulation of cystic fibrosis nasal polyp mast cells. J Pathol 166:395–404. doi:10.1002/path.1711660412

    Article  PubMed  Google Scholar 

  15. Wu H, Song Z, Givskov M et al (2001) Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection. Microbiology 147:1105–1113

    PubMed  CAS  Google Scholar 

  16. Metz M, Grimbaldeston MA, Nakae S et al (2007) Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev 217:304–328. doi:10.1111/j.1600-065X.2007.00520.x

    Article  PubMed  CAS  Google Scholar 

  17. Erickson DL, Endersby R, Kirkham A et al (2002) Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect Immun 70:1783–1790. doi:10.1128/IAI.70.4.1783-1790.2002

    Article  PubMed  CAS  Google Scholar 

  18. Singh PK, Schaefer AL, Parsek MR et al (2000) Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407:762–764. doi:10.1038/35037627

    Article  PubMed  CAS  Google Scholar 

  19. Charlton TS, de Nys R, Netting A et al (2000) A novel and sensitive method for the quantification of N-3-oxoacyl homoserine lactones using gas chromatography-mass spectrometry: application to a model bacterial biofilm. Environ Microbiol 2:530–541. doi:10.1046/j.1462-2920.2000.00136.x

    Article  PubMed  CAS  Google Scholar 

  20. Rumbaugh KP (2007) Convergence of hormones and autoinducers at the host/pathogen interface. Anal Bioanal Chem 387:425–435. doi:10.1007/s00216-006-0694-9

    Article  PubMed  CAS  Google Scholar 

  21. Chhabra SR, Harty C, Hooi DS et al (2003) Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-l-homoserine lactone as immune modulators. J Med Chem 46:97–104. doi:10.1021/jm020909n

    Article  PubMed  CAS  Google Scholar 

  22. Chun CK, Ozer EA, Welsh MJ et al (2004) Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway epithelia. Proc Natl Acad Sci USA 101:3587–3590. doi:10.1073/pnas.0308750101

    Article  PubMed  CAS  Google Scholar 

  23. Shiner EK, Terentyev D, Bryan A et al (2006) Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell Microbiol 8:1601–1610. doi:10.1111/j.1462-5822.2006.00734.x

    Article  PubMed  CAS  Google Scholar 

  24. Horikawa M, Tateda K, Tuzuki E et al (2006) Synthesis of Pseudomonas quorum-sensing autoinducer analogs and structural entities required for induction of apoptosis in macrophages. Bioorg Med Chem Lett 16:2130–2133. doi:10.1016/j.bmcl.2006.01.054

    Article  PubMed  CAS  Google Scholar 

  25. Tateda K, Ishii Y, Horikawa M et al (2003) The Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone accelerates apoptosis in macrophages and neutrophils. Infect Immun 71:5785–5793. doi:10.1128/IAI.71.10.5785-5793.2003

    Article  PubMed  CAS  Google Scholar 

  26. Li L, Hooi D, Chhabra SR et al (2004) Bacterial N-acylhomoserine lactone-induced apoptosis in breast carcinoma cells correlated with down-modulation of STAT3. Oncogene 23:4894–4902

    Article  PubMed  CAS  Google Scholar 

  27. Pearce FL (1985) Calcium and mast cell activation. Br J Clin Pharmacol 20(Suppl 2):267S–274S

    PubMed  CAS  Google Scholar 

  28. Giorgi C, Romagnoli A, Pinton P et al (2008) Ca2+ signaling, mitochondria and cell death. Curr Mol Med 8:119–130. doi:10.2174/156652408783769571

    Article  PubMed  CAS  Google Scholar 

  29. Butterfield JH, Weiler D, Dewald G et al (1988) Establishment of an immature mast cell line from a patient with mast cell leukemia. Leuk Res 12:345–355. doi:10.1016/0145-2126(88)90050-1

    Article  PubMed  CAS  Google Scholar 

  30. Brown JM, Wilson TM, Metcalfe DD (2008) The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin Exp Allergy 38:4–18

    PubMed  CAS  Google Scholar 

  31. Cole N, Bao S, Stapleton F et al (2003) Pseudomonas aeruginosa keratitis in IL-6-deficient mice. Int Arch Allergy Immunol 130:165–172. doi:10.1159/000069006

    Article  PubMed  CAS  Google Scholar 

  32. Sadikot RT, Blackwell TS, Christman JW et al (2005) Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med 171:1209–1223. doi:10.1164/rccm.200408-1044SO

    Article  PubMed  Google Scholar 

  33. Koch C, Hoiby N (1993) Pathogenesis of cystic fibrosis. Lancet 341:1065–1069. doi:10.1016/0140-6736(93)92422-P

    Article  PubMed  CAS  Google Scholar 

  34. Malaviya R, Ikeda T, Ross E et al (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature 381:77–80

    Article  PubMed  CAS  Google Scholar 

  35. Echtenacher B, Mannel DN, Hultner L (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381:75–77. doi:10.1038/381075a0

    Article  PubMed  CAS  Google Scholar 

  36. Jenkins CE, Swiatoniowski A, Power MR et al (2006) Pseudomonas aeruginosa-induced human mast cell apoptosis is associated with up-regulation of endogenous Bcl-xS and down-regulation of Bcl-xL. J Immunol 177:8000–8007

    PubMed  CAS  Google Scholar 

  37. Sun G, Liu F, Lin TJ (2005) Identification of Pseudomonas aeruginosa-induced genes in human mast cells using suppression subtractive hybridization: up-regulation of IL-8 and CCL4 production. Clin Exp Immunol 142:199–205. doi:10.1111/j.1365-2249.2005.02909.x

    Article  PubMed  CAS  Google Scholar 

  38. Lin TJ, Maher LH, Gomi K et al (2003) Selective early production of CCL20, or macrophage inflammatory protein 3alpha, by human mast cells in response to Pseudomonas aeruginosa. Infect Immun 71:365–373. doi:10.1128/IAI.71.1.365-373.2003

    Article  PubMed  CAS  Google Scholar 

  39. Lin TJ, Garduno R, Boudreau RT et al (2002) Pseudomonas aeruginosa activates human mast cells to induce neutrophil transendothelial migration via mast cell-derived IL-1 alpha and beta. J Immunol 169:4522–4530

    PubMed  CAS  Google Scholar 

  40. Pearson JP, Feldman M, Iglewski BH et al (2000) Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection. Infect Immun 68:4331–4334. doi:10.1128/IAI.68.7.4331-4334.2000

    Article  PubMed  CAS  Google Scholar 

  41. Telford G, Wheeler D, Williams P et al (1998) The Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-l-homoserine lactone has immunomodulatory activity. Infect Immun 66:36–42

    PubMed  CAS  Google Scholar 

  42. Saleh A, Figarella C, Kammouni W et al (1999) Pseudomonas aeruginosa quorum-sensing signal molecule N-(3-oxododecanoyl)-l-homoserine lactone inhibits expression of P2Y receptors in cystic fibrosis tracheal gland cells. Infect Immun 67:5076–5082

    PubMed  CAS  Google Scholar 

  43. Smith RS, Kelly R, Iglewski BH et al (2002) The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J Immunol 169:2636–2642

    PubMed  CAS  Google Scholar 

  44. Ritchie AJ, Jansson A, Stallberg J et al (2005) The Pseudomonas aeruginosa quorum-sensing molecule N-3-(oxododecanoyl)-l-homoserine lactone inhibits T-cell differentiation and cytokine production by a mechanism involving an early step in T-cell activation. Infect Immun 73:1648–1655. doi:10.1128/IAI.73.3.1648-1655.2005

    Article  PubMed  CAS  Google Scholar 

  45. Wagner C, Zimmermann S, Brenner-Weiss G et al (2006) The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN) Anal Bioanal Chem

  46. Zimmermann S, Wagner C, Muller W et al (2006) Induction of neutrophil chemotaxis by the quorum-sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Infect Immun 74:5687–5692. doi:10.1128/IAI.01940-05

    Article  PubMed  CAS  Google Scholar 

  47. Wagner C, Zimmermann S, Brenner-Weiss G et al (2007) The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN). Anal Bioanal Chem 387:481–487. doi:10.1007/s00216-006-0698-5

    Article  PubMed  CAS  Google Scholar 

  48. Kravchenko VV, Kaufmann GF, Mathison JC et al (2006) N-(3-oxo-acyl) homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways. J Biol Chem 281:28822–28830. doi:10.1074/jbc.M606613200

    Article  PubMed  CAS  Google Scholar 

  49. Hotchkiss RS, Dunne WM, Swanson PE et al (2001) Role of apoptosis in Pseudomonas aeruginosa pneumonia. Science 294:1783. doi:10.1126/science.294.5548.1783a

    Article  PubMed  CAS  Google Scholar 

  50. Lunderius C, Xiang Z, Nilsson G et al (2000) Murine mast cell lines as indicators of early events in mast cell and basophil development. Eur J Immunol 30:3396–3402. doi:10.1002/1521-4141(2000012)30:12<3396::AID-IMMU3396>3.0.CO;2-O

    Article  PubMed  CAS  Google Scholar 

  51. Ohtsu H, Kuramasu A, Suzuki S et al (1996) Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. J Biol Chem 271:28439–28444. doi:10.1074/jbc.271.45.28439

    Article  PubMed  CAS  Google Scholar 

  52. Moser C, Jensen PO, Kobayashi O et al (2002) Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response. Clin Exp Immunol 127:206–213. doi:10.1046/j.1365-2249.2002.01731.x

    Article  PubMed  CAS  Google Scholar 

  53. Hooi DS, Bycroft BW, Chhabra SR et al (2004) Differential immune modulatory activity of Pseudomonas aeruginosa quorum-sensing signal molecules. Infect Immun 72:6463–6470. doi:10.1128/IAI.72.11.6463-6470.2004

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation of China (30571647), China National 973 project (MOST, 2007CB512900). We thank Professor Zhong, RQ (Changzheng Hospital, Shanghai, China) for kindly providing human mast cell line HMC-1.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jianxin Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, H., Wang, L., Ye, L. et al. Influence of Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone on mast cells. Med Microbiol Immunol 198, 113–121 (2009). https://doi.org/10.1007/s00430-009-0111-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00430-009-0111-z

Keywords

Navigation