Journal article

Publication year: 2013

Pages: 2094-2108

Journal: The American Journal of Pathology

Volume number: 182

Issue number: 6

ISSN: 0002-9440

eISSN: 1525-2191

Open access status: Bronze

DOI Link: https://doi.org/10.1016/j.ajpath.2013.02.013

Publisher: Elsevier

Abstract: 
Mast cell (MC) accumulation has been demonstrated in the Lungs of idiopathic pulmonary fibrosis.(IPF) patients. Mediators released from MCs may regulate tissue remodeling processes, thereby contributing to IPF pathogenesis. We investigated the role of MC-fibroblast interaction in the progression of lung fibrosis. Increased numbers of activated MCs, in close proximity to fibroblast foci and alveolar type II cells, were observed in IPF lungs. Correspondingly elevated tryptase Levels were detected in IPF lung tissue samples. Coculture of human lung MCs with human Lung fibroblasts (HLFs) induced MC activation, as evinced by tryptase release, and stimulated HLF proliferation; IPF HLFs exhibited a significantly higher growth rate, compared with control. Tryptase stimulated FILE growth in a PAR-2/PKC-alpha/Raf-1/p44/42 dependent manner and potentiated extracellular matrix production, but independent of PKC-alpha, Raf-1, and p44/42 activities. Proproliferative properties of tryptase were attenuated by knockdown or pharmacological inhibition of PAR-2, PKC-alpha, Raf-1, or p44/42. Expression of transmembrane SCF, but not soluble SCF, was elevated in IPF lung tissue and in fibroblasts isolated from IPF lungs. Coculture of IPF HLFs with MCs enhanced MC survival and proliferation. These effects were cell-contact dependent and could be inhibited by application of anti-SCF antibody or CD117 inhibitor. Thus, fibroblasts and MCs appear to work in concert to perpetuate fibrotic processes and so contribute to Lung fibrosis progression.

Harvard Citation style: Wygrecka, M., Dahal, B., Kosanovic, D., Petersen, F., Taborski, B., von Gerlach, S., et al. (2013) Mast Cells and Fibroblasts Work in Concert to Aggravate Pulmonary Fibrosis Role of Transmembrane SCF and the PAR-2/PKC-α/Raf-1/p44/42 Signaling Pathway, The American Journal of Pathology, 182(6), pp. 2094-2108. https://doi.org/10.1016/j.ajpath.2013.02.013

APA Citation style: Wygrecka, M., Dahal, B., Kosanovic, D., Petersen, F., Taborski, B., von Gerlach, S., Didiasova, M., Zakrzewicz, D., Preissner, K., Schermuly, R., & Markart, P. (2013). Mast Cells and Fibroblasts Work in Concert to Aggravate Pulmonary Fibrosis Role of Transmembrane SCF and the PAR-2/PKC-α/Raf-1/p44/42 Signaling Pathway. The American Journal of Pathology. 182(6), 2094-2108. https://doi.org/10.1016/j.ajpath.2013.02.013