Abstract
Rationale: Mast cell (MC) activation has been implicated in the pathogenesis of inflammatory lung diseases. Among the MC-derived mediators, MC chymase is involved in the processes such as activation of TGF-β and formation of collagen fibrils. The literature suggests that chymase may contribute to the pathogenesis of pulmonary interstitial remodeling; however, a systematic investigation is still missing.
Methods: Lung tissues obtained from donors and patients with idiopathic pulmonary fibrosis (IPF) were formalin-fixed and paraffin-embedded, followed by toluidine blue staining for MCs and by immunostaining for chymase. The total, perivascular and interstitial MC and chymase-positive MC (CMC) number in each section was evaluated by using a light microscopy and computerized morphometric system. Also, MCs were separated as granulated and degranulated (activated) and index of granulation (IOG) (number of granulated/number of degranulated MCs) was determined.
Results: The quantification of pulmonary MCs and CMCs revealed that their population was about 6 and 8 folds higher in IPF patients, as compared with donors. There was a preponderance of perivascular MCs and CMCs in IPF lungs (p<0.05 versus donor lungs). Furthermore, we found that there was about 8 fold decrease of IOG in IPF patients as compared with donors. Finally, there was a strong accumulation of both MCs and CMCs in interstitial regions of the tissues (∼65%) in comparison with other regions of the lungs.
Conclusion: The findings suggest that chymase released from activated MCs may be involved in the pathogenesis of IPF. Further investigations will unravel the underlying pathomechanism and substantiate chymase as a potential target for future therapeutic strategies.
- © 2011 ERS