Unit of Lung Biology, Department of Experimental Medical Sciences, Lund University, BMC C12, 221 84, Lund, Sweden.
Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Lund, Sweden.
Cell Commun Signal. 2018 Sep 15;16(1):59. doi: 10.1186/s12964-018-0269-3.
Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation.
Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells.
The migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration.
Mast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.
肥大细胞可能会激活成纤维细胞，并促进肺部的重塑过程。然而，这些作用的机制仍需要进一步研究。成纤维细胞是进行中重塑过程的主要调节者。成纤维细胞表达的蛋白酶激活受体 2（PAR2）可被丝氨酸蛋白酶（如肥大细胞介质胰蛋白酶）激活。本研究的目的是研究肥大细胞，特别是肥大细胞胰蛋白酶对成纤维细胞迁移的影响，以及 PAR2 激活的作用。
培养人肺成纤维细胞（HFL-1），与人外周血衍生的肥大细胞或 LAD2 肥大细胞共培养，并分别用 LAD2 细胞的条件培养基或胰蛋白酶刺激。还对 IgE/抗 IgE 在共培养系统中对肥大细胞的免疫刺激进行了分析。通过用 PAR2 拮抗剂 P2pal-18S 预处理，研究了肥大细胞和肥大细胞胰蛋白酶对成纤维细胞迁移作用的 PAR2 激活的重要性。分析了 PAR2 在成纤维细胞和肥大细胞上的表达。
血液来源的肥大细胞（p<0.02）、LAD2 细胞（p<0.001）、条件培养基（p<0.05）和胰蛋白酶（p<0.006）均可增强 HFL-1 细胞的迁移能力。P2pal-18S 降低了肥大细胞（p<0.001）和胰蛋白酶（p<0.001）诱导的迁移，并且验证了 PAR2 在 HFL-1 细胞中的表达。用 IgE/抗 IgE 免疫刺激的肥大细胞对成纤维细胞迁移没有进一步的影响。
肥大细胞和肥大细胞介质胰蛋白酶可能通过 PAR-2 激活在诱导肺成纤维细胞迁移中起关键作用，这可能有助于慢性肺部疾病中的重塑过程。
