Differential effect of M1 and M2 macrophages on airway epithelial cell innate immunity and wound repair

Abstract

The interaction between airway epithelial cells with immune and structural cells in the lung is complex and insufficiently studied due to a lack of an appropriate in vitro model. We designed an in vitro model using well-differentiated human primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC). These cells were co-cultured with human CD14+ monocyte-derived pro-inflammatory (Mφ1) or anti-inflammatory, pro-repair (Mφ2) macrophages, resp. Co-culture of ALI-PBEC with LPS-activated Mφ1 induced mRNA expression of hBD-2, IL-8 and IL-6 (36-, 11- and 18-fold increase resp. compared to ALI-PBEC only) at 24h, whereas this response was lower upon co-culture with LPS-stimulated Mφ2 (15-, 2- and 4-fold increase resp.). Furthermore, epithelial wound repair was accelerated by co-culture with both Mφ1 and Mφ2 (100% wound closure at 48h after wounding vs. 60% wound closure in ALI-PBEC alone), but remarkably the effect of Mφ1 cells was more pronounced at earlier time points than that of Mφ2. We demonstrate that this model is suitable for studying macrophage-epithelial interactions, and show that especially Mφ1 are capable of enhancing innate immune responses and accelerating wound repair in ALI-PBEC.