Alveolar macrophages modulate allergic inflammation in a murine model of asthma

Bo-Ram Bang,Heung-Woo Park,Eunyoung Chun,Soo-Yeon Lee,Hyun-Seung Lee,You-Young Kim,Kyung-Up Min,Sang-Heon Cho,Eun-Jin Shim

doi:10.3858/emm.2011.43.5.028

Bo-Ram Bang, Heung-Woo Park + Show 7 more

Open Access

https://doi.org/10.3858/emm.2011.43.5.028

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Abstract

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.

Highlights

Alveolar macrophages (AMs) are the most abundant cells in the alveolar spaces and conducting airways, and are known to be involved in immune homeostasis in the respiratory tract (Wissinger et al, 2009)
We demonstrated that AMdepletion after sensitization significantly increased the number of eosinophilis and lymphocytes, and the concentrations of IL-4, IL-5, and GM-CSF in bronchoalveolar lavage (BAL) fluid in a murine model of asthma
The observations, in conjunction with a previous report that unsensitized AMs can protect against development of airway hyperresponsiveness (Careau et al, 2006), suggest that AMs may have an important role in the development of asthma

Summary

Introduction

Alveolar macrophages (AMs) are the most abundant cells in the alveolar spaces and conducting airways, and are known to be involved in immune homeostasis in the respiratory tract (Wissinger et al, 2009). Asthma is a disease characterized by immune-mediated airway inflammation. Several reports have suggested that AMs suppress allergenspecific immune response and airway inflammation (Thepen et al, 1991, 1992; Tang et al, 2001; Careau et al, 2010). This property seems to be dependent on the functional status of AMs. Sensitized AMs promote eosinophilic airway inflammation (Moon et al, 2007) and take part in acute asthma exacerbation by stimulating CD4-positive T cells to secrete cytokines (Herbert et al, 2010). A recent report has shown that allergen sensitization modulates AM function and only unsensitized AMs protect against development of airway hyperresponsiveness (Careau et al, 2006)

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