Histological Characterization of Mast Cell Chymase in Patients with Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease

PVRI Member Authors: Djuro Kosanovic, Michael Seimetz, Irwin Reiss, Ardeschir Ghofrani, Norbert Weissmann, Werner Seeger, Ralph T. Schermuly

Abstract

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 significantly 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.

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Topics

COPD
Monocytes/ Macrophages/ Neutrophils/ Dendritic Cells/ Mast Cells
Pulmonary Arterial Hypertension

Authors

Djuro Kosanovica, Bhola Kumar Dahala, Dorothea Maren Peters, Michael Seimetz, Malgorzata Wygrecka, Katrin Hoffmann, Jochen Antel, Irwin Reiss, Hossein Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly

Published in:

Pulmonary Circulation Vol 4: No 1 cover image

March 2014

Pulmonary Circulation Vol 4: No 1

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