Histological characterization of mast cell chymase in patients with pulmonary hypertension and chronic obstructive pulmonary disease
Our previous findings demonstrated an increase in pulmonary mast cells (MCs) in idiopathic pulmonary arterial hypertension (IPAH). Also, literature suggests a potential role for MCs in chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of lungs from patients is still needed. We systematically investigated the presence/expression of MCs/MC chymase in the lungs of IPAH and COPD patients by (immuno)histochemistry and subsequent quantification. We found that total and perivascular chymase-positive MCs were significantly higher in IPAH patients than in donors. In addition, chymase-positive MCs were located in proximity to regions with prominent expression of big-endothelin-1 in the pulmonary vessels of IPAH patients. Total and perivascular MCs around resistant vessels were augmented and a significant majority of them were degranulated (activated) in COPD patients. While the total chymase-positive MC count tended to increase in COPD patients, the perivascular number was significant y enhanced in all vessel sizes analyzed. Surprisingly, MC and chymase-positive MC numbers positively correlated with better lung function in COPD. Our findings suggest that activated MCs, possibly by releasing chymase, may contribute to pulmonary vascular remodeling in IPAH. Pulmonary MCs/chymase may have compartment-specific (vascular vs. airway) functions in COPD. Future studies should elucidate the mechanisms of MC accumulation and the role of MC chymase in pathologies of these severe lung diseases.
|Keywords||Chronic obstructive pulmonary disease, Chymase, Idiopathic pulmonary arterial hypertension, Mast cells|
|Persistent URL||dx.doi.org/10.1086/675642, hdl.handle.net/1765/101238|
Kosanovic, D, Dahal, B.K, Peters, D.M. (Dorothea Maren), Seimetz, M. (Michael), Wygrecka, M, Hoffmann, K. (Katrin), … Schermuly, R.T. (2014). Histological characterization of mast cell chymase in patients with pulmonary hypertension and chronic obstructive pulmonary disease. Pulmonary Circulation, 4(1), 128–136. doi:10.1086/675642