Pathologic reparation of the stem cell niche zones of respiratory acini in idiopathic pulmonary fibrosis

The aim. Investigating morphological and molecular characteristics of injury and reparation of the stem cell niche (SCN) zones in the respiratory acini and determining a role of these changes for the pathogenesis of idiopathic pulmonary fibrosis (IPF) / usual interstitial pneumonia (UIP). Methods. Surgical transthoracic (n = 71) and transbronchial (n = 47) lung biopsy specimen from 118 patients were investigated. Bronchiolar carcinoma occurring against the background of ILF was diagnosed in 13 cases. Serial paraffin sections were stained with hematoxylin and eosin and Van Gieson picrofuchsin; immunohistochemical reactions were used to detect MMP-1, -2, -7, TIMP-4, PCNA, PDGF, EGF, FGF-b, desmin (Dsm), vimentin (Vimentin), SMA (LabVision, 1 : 100), Apo-Cas (Novocastra, 1 : 100), TGF-b, TNF-a, CD 34, CK-7, -18, Oct-4 and CD-117 (DAKO, 1 : 50), CD68, (DAKO, 1 : 100), CK-5 (Biogenesis, 1 : 200), CK-6, -19 (Uni-Heidelberg, 1: 100). Biotinylated antibodies against mouse and rabbit immunoglobulins (Dako LSAB + KIT, Peroxidase) were used as secondary antibodies. All quantitative and semi-quantitative data were analyzed with variational statistics. Results. Involvement of NSC zones of the lung tissue plays the key role in pathogenesis and morphogenesis of IPF / UIP. This leads to deficient reparation. Disorders of mesenchymal-epithelial transformation / epithelial-mesenchymal transformation (MET / EMT) are likely to be a basis for insufficient reparation in UIP. This is supported by appearance of cells with myofibroblast phenotype expressing both markers of mesenchymal and epithelial differentiation and stem cell markers in the SCN zones. Conclusion. Cells with myofibroblast phenotype could be considered as markers of pathologic reparation following MET program failure. Subsequently, MET program failure in UIP could lead to the development of «honey-comb» disorders in the lungs and also to lung carcinoma development.

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