Differences in macrophage polarization in allergic inflammation (HYP6P.271)

Abstract

Abstract Lung macrophages (alternatively activated or “M2” macrophages) are critical modulators of the severity of pulmonary inflammation. M2 macrophages differentiate from mature macrophages upon exposure to Th2 cytokines, IL-4 and IL-13, abundant during allergic lung inflammation. Greater numbers of M2 macrophages were found in the lungs of female mice than male mice and in patients with asthma compared to healthy controls. SOCS1 and SOCS3 are negative regulators that control M1/M2 polarization of macrophages and they may be regulated by estrogen. We hypothesize that monocytes from asthmatic females are more responsive to IL-4/IL-13 than those from asthmatic men and that estrogen increases and androgen diminishes monocyte responses to IL-4 and IL-13. To compare sex differences in IL-4/IL-13 responses in monocytes, we purified and stimulated monocytes from male and female allergic and healthy donors with IL-4 and IL-13. We found high levels of SOCS3 in monocytes from allergic donors compared to healthy controls after IL-4 stimulation. Interestingly, expression of ERα mRNA was higher in allergic compared to healthy human macrophages, whereas ERβ and AR expression was lower. Differences in SOCS induction will provide clues to understanding sensitivity of monocyte-macrophages from allergic individuals to IL-4 and IL-13. The role of ERα, β and AR to IL-4-induced M2 macrophage polarization will help us understand why the prevalence of asthma in adult women is higher than in men.