Location of Repository

IgE alone promotes human lung mast cell survival through the autocrine production of IL-6

By Glenn Cruse, Sarah Cockerill and Peter Bradding

Abstract

Background: Mast cells play a key role in asthma and recent evidence indicates that their ongoing\ud activation in this disease is mediated, in part, via IgE in the absence of antigen. In this study we have\ud examined whether IgE alone enhances human lung mast cell (HLMC) survival.\ud Methods: Purified HLMC were cultured for 4 weeks and survival assays then performed over 10\ud days following cytokine withdrawal in the presence or absence of human myeloma IgE. Quantitative\ud real time RT-PCR was carried out to examine IL-6 mRNA expression and IL-6 protein was\ud measured in HLMC supernatants by ELISA.\ud Results: IgE alone promoted the survival of HLMC in a dose-dependent manner following cytokine\ud withdrawal. IgE-induced survival was eliminated with the addition of neutralising anti-IL-6 antibody\ud but not by the addition of neutralising anti-stem cell factor. IgE sensitisation initiated profound\ud upregulation of IL-6 mRNA in HLMC, and IL-6 concentrations were also raised in the culture\ud supernatants of IgE-exposed cells.\ud Conclusion: These data taken together suggest that IgE in the absence of antigen promotes HLMC\ud survival through the autocrine production of IL-6. This provides a further mechanism through\ud which IL-6 and IgE contribute to the pathogenesis of asthma, and through which anti-IgE therapy\ud might achieve its therapeutic effect.Peer-reviewedPublisher Versio

Publisher: BioMed Central Ltd
Year: 2008
DOI identifier: 10.1186/1471-2172-9-2
OAI identifier: oai:lra.le.ac.uk:2381/8459
Journal:

Suggested articles

Preview

Citations

  1. (2006). AM: Molecular regulation of mast cell activation. doi
  2. (2005). Bradding P: Activation of human lung mast cells by monomeric immunoglobulin E. Eur Respir J
  3. (2000). Bradding P: Adhesion of human lung mast cells to bronchial epithelium: evidence for a novel carbohydrate-mediated mechanism.
  4. (2005). Bradding P: The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med doi
  5. (1989). Cline MG: Association of asthma with serum IgE levels and skin-test reactivity to allergens. doi
  6. (2004). Early divergence of Fc epsilon receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survival. doi
  7. (2004). Fahy JV: Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med doi
  8. (1997). FL: The effect of recombinant stem cell factor on human skin and lung mast cells and basophil leukocytes. Inflammation Research doi
  9. (2003). Greenfeder S: Human cord blood-derived mast cells synthesize and release I-309 in response to IgE. Life Sci doi
  10. (2006). Holgate ST: The role of the mast cell in the pathophysiology of asthma. doi
  11. (1996). Hultner L: Critical protective role of mast cells in a model of acute septic peritonitis. Nature doi
  12. (2005). I: Death of a dogma or enforcing the artificial: monomeric IgE binding may initiate mast cell response by inducing its receptor aggregation. doi
  13. (2004). IgE aloneinduced actin assembly modifies calcium signaling and degranulation in RBL-2H3 mast cells. doi
  14. (2004). LB: Neutralizing endogenous IL-6 renders mast cells of the MCT type from lung, but not the MCTC type from skin and lung, susceptible to human recombinant IL-4-induced apoptosis. doi
  15. (2005). Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J Exp Med doi
  16. (2005). Mast cell survival and activation by IgE in the absence of antigen: a consideration of the biologic mechanisms and relevance. doi
  17. (2006). Mast cells are required for normal healing of skin wounds in mice. doi
  18. (2004). Masukawa T: Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice. Int Immunopharmacol doi
  19. (1991). MD: Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. doi
  20. (1995). MJ: Relationship between serum IgE and airway responsiveness in adults with asthma. doi
  21. (2008). Monomeric IgE and lipopolysaccharide synergistically prevent mast-cell apoptosis. Biochem Biophys Res Commun doi
  22. (1995). Nakahata T: Effects of T-helper 2-type cytokines, interleukin-3 (IL-3), IL-4, IL-5, and IL-6 on the survival of cultured human mast cells. Blood
  23. Primer3 on the WWW for general users and for biologist programmers. In Bioinformatics Methods and Protocols: Methods in Molecular Biology. doi
  24. (2005). Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen. Blood doi
  25. (1998). Roche WR: Human mast cells express stem cell factor. doi
  26. (2001). Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods doi
  27. (2001). Selective down-regulation of high-affinity IgE receptor (FcepsilonRI) alpha-chain messenger RNA among transcriptome in cord blood-derived versus adult peripheral blood-derived cultured human mast cells. Blood doi
  28. (1994). SJ: The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis.
  29. (2003). T: Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcepsilonRI. doi
  30. (2001). T: Regulation of mast cell survival by IgE. Immunity doi
  31. (2005). Tanaka S: Critical role of protein kinase C betaII in activation of mast cells by monomeric IgE. doi
  32. (2002). The role of SHIP in mast cell degranulation and IgE-induced mast cell survival. Immunol Lett doi
  33. (2006). Tkaczyk C: Integrated signalling pathways for mast-cell activation. Nat Rev Immunol doi
  34. (1996). Total serum IgE is associated with asthma independently of specific IgE levels. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.