Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and polarized primary monocyte-derived macrophages. Using this coculture, we studied the contribution of macrophages to epithelial innate immunity, wound healing capacity, and epithelial exposure to whole cigarette smoke (WCS). Coculture of ALI-PBEC with lipopolysaccharide (LPS)-activated M(GM-CSF) macrophages increased the expression of DEFB4A, CXCL8, and IL6 at 24 h in the ALI-PBEC, whereas LPS-activated M(M-CSF) macrophages only increased epithelial IL6 expression. Furthermore, wound repair was accelerated by coculture with both activated M(GM-CSF) and M(M-CSF) macrophages, also following WCS exposure. Coculture of ALI-PBEC and M(GM-CSF) macrophages resulted in increased CAMP expression in M(GM-CSF) macrophages, which was absent in M(M-CSF) macrophages. CAMP encodes LL-37, an antimicrobial peptide with immune-modulating and repair-enhancing activities. In conclusion, dynamic crosstalk between ALI-PBEC and macrophages enhances epithelial innate immunity and wound repair, even upon concomitant cigarette smoke exposure.
J Innate Immun

中文翻译：

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M（GM-CSF）和M（M-CSF）巨噬细胞对气道上皮先天免疫和伤口修复的调节。

气道上皮细胞和巨噬细胞参与对外部有害刺激的炎症反应，这可能导致上皮损伤。受伤后，上皮细胞和巨噬细胞协同作用，以确保快速恢复上皮完整性。上皮修复过程中这些细胞类型之间相互作用的性质尚不完全清楚。我们使用体外人共培养模型，在气液界面（ALI-PBEC）和极化的原代单核细胞衍生的巨噬细胞上培养原代支气管上皮细胞。使用这种共培养，我们研究了巨噬细胞对上皮先天免疫，伤口愈合能力以及上皮暴露于整支香烟烟雾（WCS）的贡献。ALI-PBEC与脂多糖（LPS）激活的M（GM-CSF）巨噬细胞的共培养可增加巨噬细胞的表达DEFB4A，CXCL8和IL6在ALI-PBEC中在24小时内，而LPS激活的M（M-CSF）巨噬细胞仅增加上皮IL6的表达。此外，WCS暴露后，通过与活化的M（GM-CSF）和M（M-CSF）巨噬细胞共培养来加速伤口修复。ALI-PBEC和M（GM-CSF）巨噬细胞的共培养导致M（GM-CSF）巨噬细胞中CAMP表达的增加，而M（M-CSF）巨噬细胞中则没有。CAMP编码LL-37，一种具有免疫调节和增强修复活性的抗菌肽。总之，即使伴随着香烟烟雾暴露，ALI-PBEC与巨噬细胞之间的动态串扰也会增强上皮先天免疫和伤口修复。
免疫学杂志