Abstract
BackgroundMast 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.MethodsHuman 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.ResultsThe 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.ConclusionsMast 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.
Highlights
Mast cells may activate fibroblasts and contribute to remodeling processes in the lung
peripheral blood derived mast cells (PBdMC) were positive for tryptase, which is the main mast cell protease released during degranulation [30] (Fig. 1a)
We have demonstrated for the first time that mast cells (PBdMC and LAD2) and the mast cell mediator tryptase enhance the migratory capacity of human lung fibroblasts (HFL-1)
Summary
Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. The objective in this study was to investigate the effects of mast cells and mast cell tryptase on fibroblast migration and the role of PAR2 activation. Bagher et al Cell Communication and Signaling (2018) 16:59 morphological features of both fibroblasts and smooth muscle cells These cells are increased in number in chronic lung diseases and have been suggested to contribute to tissue remodeling processes [10]. Previous studies imply that mast cell mediators are involved in fibroblast differentiation into myofibroblasts [11] Mast cell mediators, such as tryptase, may induce ECM synthesis, migration and proliferation in fibroblasts, resulting in airway remodeling. Despite evidence that mast cells activate fibroblasts and contribute to remodeling, the mechanism for this interaction is poorly understood For this reason, this study was designed to test the hypothesis that mast cells influence the migratory capacity of fibroblasts through PAR2
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