Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-γ expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 μg) induced type 2 asthma phenotypes, i.e., airway hyperresponsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 μg) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-γ-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-α expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-α receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.

The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-CSF in BAL fluid. These changes were significantly ameliorated only by adoptive transfer of unsensitized AMs, not by sensitized AMs. In addition, in vitro allergen stimulation of AMs resulted in their gaining the ability to produce inflammatory cytokines, such as IL-1β, IL-6 and TNF-α, and losing the ability to suppress GM-CSF concentrations in BAL fluid. These findings suggested that AMs worked probably through GM-CSF-dependent mechanisms, although further confirmatory experiments are needed. Our results indicate that the role of AMs in the context of airway inflammation should be re-examined.

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Series results for the anisotropic Ising model are analysed by investigating the logarithmic derivative of the susceptibility. If the odd and even coefficients are extrapolated separately, results consistent with scaling and universality predictions are obtained.

Reactive oxygen species (ROS) are known aggravating factors for airway inflammation in asthma. Glutathione S-transferases (GSTs) detoxify ROS and toxic compounds in environmental exposures. However, little is known about the regulation of GST and expression of GST subtypes in asthma. The aim of this study was to evaluate how GSTs are regulated in asthma. We observed total GST activity and expression of GST subtypes in murine asthma models and GST expressions in induced sputum cells of asthmatics. Total GST activity was increased in BAL fluids of OVA-treated murine asthma model. GSTP and GSTA are highly expressed in peribronchiolar mononuclear inflammatory cells and epithelial cells in OVA-treated mice. GSTM are expressed in epithelial cells in both OVA and PBS-treated groups. GSTP1 mRNA expression was increased in the lung of OVA-treated mice compared with PBS-treated mice. GSTA1, GSTM1, and GSTT1 mRNA expressions were not different between both groups. GSTA1 mRNA expression was increased in induced sputum cells of asthmatics compared with healthy controls. GSTP1, GSTM1, and GSTT1 mRNA expressions were not different between asthmatics and healthy controls. In asthmatics, GSTP1 and GSTA1 mRNA expressions were higher in induced sputum cells of asthmatics with PC20 ≤ 4 mg/ml than those with PC20 > 4 mg/ml. GSTM1 and GSTT1 mRNA expressions were not different between two groups. These findings suggest that GSTs are upregulated in the airways of asthmatics in response to increased oxidative stress. GSTP and GSTA are thought to play an important role in protecting the airways of asthmatics compared with GSTM and GSTT.