Objective: To investigate the protein and gene expression in bronchoalveolar lavage cells and open lung biopsies from patients with IPF.
Methods: The immunohistochemical methods were used to analyze the expression of PDGF, TGF-beta in bronchoalveolar lavage cells of patients with IPF. For open lung biopsies, both immunohistochemistry and in situ hybridization were used.
Results: In specimens of bronchoalveolar lavage fluid, PDGF-AA, PDGF-BB, TGF-beta were localized to alveolar macrophages in patients with IPF. Though there were no differences between IPF and sarcoidosis in terms of the staining intensity (2.5 - 3.0) or number of positive cells 81% - 90%, the number of such cells were less in the control (0 - 1.7, 25% - 32% respectively). Evaluation of open lung biopsies from patients with IPF showed that PDGF, TGF-beta proteins were localized to hyperplastic bronchio-alveolar epithelial cells (2.4 - 3.7, in control 0), alveolar macrophages (2.9 - 3.7, in control 0.8 - 1.3), fibroblasts (3.0 - 3.6, in control 2.7 - 2.8), vascular smooth muscle cells, vascular endothelial cells, and fibroblast-like cells surrounding pulmonary vessels (2.7 - 4.0, in control 2.1 - 2.9). In situ hybridization results were consistent with that of immunohistochemistry except that PDGF and TGF-beta mRNA transcripts were not detected in bronchio-alveolar epithelial cells. In control lungs, however, both ISH and IHC revealed that PDGF and TGF-beta were only present in the pleura and in fibroblast-like cells surrounding pulmonary vessels.
Conclusions: PDGF and TGF-beta, which interplay with pulmonary mesenchymal cells, are involved in fibroplasia and deposition of extracellular matrix as well as angiogenesis and epithelial cell repopularization.