HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Mast cell chymase: an indispensable instrument in the pathological symphony of idiopathic pulmonary fibrosis?

Djuro Kosanovic1*, Bhola Kumar Dahal1*, Malgorzata Wygrecka1, Irwin Reiss2, Andreas Günther1, Hossein Ardeschir Ghofrani1, Norbert Weissmann1, Friedrich Grimminger1, Werner Seeger1,3, Ralph Theo Schermuly1 and Gamal-Andre Banat1

1Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany , 2Division of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands and 3Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany
*both authors contributed equally to this work.

Offprint requests to: Ralph Theo Schermuly, PhD, Chair for Pulmonary Pharmacotherapy, UGMLC, Justus-Liebig University, Aulweg 130, 35392 Giessen, Germany. e-mail: ralph.schermuly@innere.med.uni-giessen.de


Summary. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease with no known etiology and treatment options. The hallmarks of the histopathology, which is characteristic of usual interstitial pneumonia (UIP) pattern, include interstitial fibrosis, honeycomb changes and fibroblast foci that develop owing to fibroblast proliferation and excessive matrix deposition. Although the complete patho-mechanism is not yet understood, several molecular culprits, including transforming growth factor (TGF)-ß, Angiotensin (Ang) II, endothelin (ET)-1, matrix metalloproteinases (MMPs) and cytokines have been identified. IPF is increasingly believed to be an epithelial-driven disease; however, the literature does support an implication of altered immune response and inflammatory processes in the onset or progression of the disease. Mast cells (MCs) are multifunctional tissue resident cells involved in the inflammatory and immune response. An increasing body of evidence suggests a role of MCs and their mediator chymase in the pathology of IPF. With regard to the underlying mechanisms, it is conceivable that MC chymase may function via activation or processing of factors such as proteases, cytokines and growth factors. In this review, we will discuss how MC chymase is linked to and can potentially contribute to the development of IPF. Moreover, the findings from animal model studies will be discussed to highlight the chymase inhibitors as a promising strategy for the treatment of pulmonary fibrosis
. Histol Histopathol 28, 691-699 (2013)

Key words: Mast cells, Chymase, Pulmonary fibrosis, Angiotensin II, TGF-ß

DOI: 10.14670/HH-28.691