Dual role of YM1+ M2 macrophages in allergic lung inflammation.

Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation during and after development of allergic lung inflammation by treating with cynaropicrin, a galectin-3 pathway inhibitor. Mice that were treated with this inhibitor of M2 polarisation during induction of allergic inflammation developed less severe eosinophilic lung inflammation and less collagen deposition around airways, while the airway α-smooth muscle actin layer was unaffected. When we treated with cynaropicrin after induction of inflammation, eosinophilic lung inflammation and collagen deposition were also inhibited though to a lesser extent. Unexpectedly, both during and after induction of allergic inflammation, inhibition of M2 polarisation resulted in a shift towards neutrophilic inflammation. Moreover, airway hyperresponsiveness was worse in mice treated with cynaropicrin as compared to allergic mice without inhibitor. These results show that M2 macrophages are associated with remodeling and development of eosinophilic lung inflammation, but prevent development of neutrophilic lung inflammation and worsening of airway hyperresponsiveness. This study suggests that macrophages contribute to determining development of eosinophilic or neutrophilic lung inflammation in asthma.