Lipopolysaccharide inhalation exacerbates allergic airway inflammation by activating mast cells and promoting Th2 responses

D. Murakami, H. Yamada, T. Yajima, A. Masuda, S. Komune, Y. Yoshikai

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background: Bacterial infection occasionally exacerbates asthma, although the cellular and molecular mechanisms have not been well defined. An involvement of mast cells has been suggested, as lipopolysaccharides (LPS)-induced cytokine production from mast cells in vitro. Objective: This study was undertaken to examine the effects of LPS inhalation on mast cell functions and allergen-specific immune responses in a murine model of asthma. Methods: Female BALB/c mice or mast cell-deficient W/Wv mice were immunized intraperitoneally with ovalbumin (OVA). Mice were challenged with aerosolized OVA or OVA with LPS daily from day 21 to day 24. Twenty-four hours after the last challenge, airway inflammation and OVA-specific immune responses were examined. Allergen-specific T cell responses were further analysed by adoptively transferring OVA-specific CD4+ T cells. Expression of chemokines in the lung was also examined. Results: LPS inhalation with OVA resulted in exacerbated airway infiltration, which was not evident in mast cell-deficient mice. IL-5 production by mast cells in the lung was enhanced by LPS inhalation. OVA-specific IgE production as well as proliferation, cytokine production and local infiltration of OVA specific T-helper lymphocytes type 2 (Th2) were also enhanced. Up-regulated expression of Th2- and/or eosinophil-attracting chemokines was observed in the lung of mice inhalated with LPS. Conclusions: LPS inhalation exacerbates airway inflammation, which is accompanied by mast cell activation and enhanced Th2 responses. These observations provide clues towards understanding the mechanisms of bacterial infection-induced exacerbation of the clinical features of asthma.

Original languageEnglish
Pages (from-to)339-347
Number of pages9
JournalClinical and Experimental Allergy
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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