Sex-dependent differences in lung inflammation and M2-macrophage responses in asthma (HYP2P.328)

Abstract

Abstract ​Asthma is a chronic airway inflammatory disease that exhibits a sex difference. Alveolar macrophages acquire an M2-phenotype in asthma and in response to IL-4 in vitro. M2 macrophages correlate with poor lung function and pathology in asthmatics. We hypothesized that macrophages from female mice are intrinsically more responsive to IL-4 than male macrophages. Western blot demonstrated greater expression of the M2-marker, Ym-1 (~14 fold), in IL-4-activated bone marrow-derived macrophages (BMM) from female mice compared to male mice. We next assessed alveolar macrophages from male and female OVA-sensitized and -challenged mice for expression of M2-markers by FACS and western blot. We measured enhanced eosinophilia and increased Ym-1 expression in alveolar macrophages from female mice compared to male mice following OVA challenge. Estrogen enhances macrophage activation but the impact on lung macrophages during asthma is poorly understood. We observed a greater percentage of macrophages in the lungs of estrogen-implanted female mice that had undergone ovariectomy, compared to placebo-implanted females, following OVA challenge. These data suggest both intrinsic and estrogen-enhanced M2 macrophage polarization in females compared to males. Understanding intrinsic and estrogen-mediated sex differences in asthma is paramount to identify novel molecular targets and improve therapeutics in women with hard-to-treat asthma.