Unit of Lung Biology, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden.
Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, 221 85 Lund, Sweden.
Int J Mol Sci. 2021 Jan 6;22(2):506. doi: 10.3390/ijms22020506.
Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.
肥大细胞在哮喘中发挥着重要作用，然而，特发性肺纤维化（IPF）中肥大细胞、成纤维细胞和上皮细胞之间的相互作用知之甚少。本研究旨在探讨肥大细胞对成纤维细胞活性和上皮细胞迁移的影响。将来自 IPF 患者和健康个体的肺成纤维细胞与 LAD2 肥大细胞共培养或用蛋白酶胰蛋白酶和糜蛋白酶刺激。将人肺成纤维细胞和肥大细胞培养在细胞培养塑料板或脱细胞化的人肺组织（支架）上，通过提供肺泡细胞外基质来创造更接近生理的环境。分析释放的介质，并评估其对上皮细胞迁移的影响。胰蛋白酶增加了成纤维细胞中血管内皮生长因子（VEGF）的释放，而与肥大细胞共培养则增加了白细胞介素 6（IL-6）和肝细胞生长因子（HGF）的释放。与在塑料上培养相比，支架培养增加了 VEGF 的释放。IL-6 减少了上皮细胞的迁移，而 HGF 和支架培养的条件培养基则促进了迁移。总之，肥大细胞和胰蛋白酶增加了成纤维细胞释放的介质，这些介质影响上皮细胞的迁移。这些数据表明，肥大细胞和胰蛋白酶在健康和肺部疾病中，成纤维细胞、上皮细胞和肺泡细胞外基质之间的相互作用中发挥作用。
