The controversial role of mast cells in fibrosis

Abstract

Fibrosis is a medical condition characterized by an excessive deposition of extracellular matrix compounds such as collagen in tissues. Fibrotic lesions are present in many diseases and can affect all organs. The excessive extracellular matrix accumulation in these conditions can often have serious consequences and in many cases be life-threatening. A typical event seen in many fibrotic conditions is a profound accumulation of mast cells (MCs), suggesting that these cells can contribute to the pathology. Indeed, there is now substantialv evidence pointing to an important role of MCs in fibrotic disease. However, investigations from various clinical settings and different animal models have arrived at partly contradictory conclusions as to how MCs affect fibrosis, with many studies suggesting a detrimental role of MCs whereas others suggest that MCs can be protective. Here, we review the current knowledge of how MCs can affect fibrosis.

Ocular Surface Fibroma: Clinical, Histopathological, and Immunohistochemical Features of 10 Cases

“…The significance of the presence of mast cells in OSF is uncertain, with some evidence that it correlates positively with the amount of collagenous stromal tissue in softtissue tumours [7]. The role of mast cells in fibrosis is also controversial, with some reports suggesting that their presence promotes fibrosis whereas some suggest their presence provides protection against fibrosis [8].…”

Ca2+ signalling in fibroblasts and the therapeutic potential of KCa3.1 channel blockers in fibrotic diseases

“…Both mast cells and fibrocytes are implicated in IPF progression and express K Ca 3.1 (Cruse et al, ; Duffy et al, ). Mast cells infiltrate the fibrotic areas of IPF lungs and interact intimately with human lung fibroblasts, with important bidirectional pro‐fibrotic interactions (Bradding & Pejler, ). K Ca 3.1 in mast cells is activated following IgE‐dependent activation and promotes degranulation (Duffy et al, ) and is required for human lung mast cell migration to diverse stimuli (Cruse et al, ).…”

“…Importantly, senicapoc was well tolerated in this model, unlike pirfenidone (unpublished).Both mast cells and fibrocytes are implicated in IPF progression and express K Ca 3.1(Cruse et al, 2011; Duffy et al, 2001). Mast cells infiltrate the fibrotic areas of IPF lungs and interact intimately with human lung fibroblasts, with important bidirectional pro-fibrotic interactions(Bradding & Pejler, 2018). K Ca 3.1 in mast cells is activated following IgE-dependent activation and promotes degranulation (Duffy…”

What we know (and don't know) about the biology and functions of mast cells and basophils

“…Piliponsky et al discuss the results of recent studies that show that mast cells can both promote host resistance to infections caused by bacteria and fungi or increase host morbidity and mortality by dysregulating protective immune responses. The controversial role of mast cells in fibrosis is reviewed by Peijler and Bradding . Many fibrotic conditions are characterized by the accumulation of mast cells, suggesting that they play a role in promoting fibrosis or limiting it.…”