Lipopolysaccharide inhalation exacerbates allergic airway inflammation by activating mast cells and promoting Th2 responses.
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/W(v) 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.
Murakami
D
D
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yamada
H
H
Yajima
T
T
Masuda
A
A
Komune
S
S
Yoshikai
Y
Y
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012141:Respiratory Tract Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D008070:Lipopolysaccharides