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

• Published in: Clinical and experimental allergy 2007-03, Vol.37 (3), p.339-347
• Main Authors: Murakami, D., Yamada, H., Yajima, T., Masuda, A., Komune, S., Yoshikai, Y.
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Allergic diseases; Animals; asthma; Asthma - immunology; Bacterial Infections - immunology; Biological and medical sciences; chemokines; cytokines; Cytokines - immunology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; lipopolysaccharide; Lipopolysaccharides - adverse effects; Lipopolysaccharides - immunology; mast cells; Mast Cells - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Respiratory Tract Infections - immunology; Th2 cells; Th2 Cells - immunology
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02633.x

Summary 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.