Interstitial pulmonary fibrosis (IPF) affects millions of individuals worldwide. Common features of this pathology are varying degrees of acute and chronic inflammation, stiffening of the lung over time and shortness of breath due to impairment of gas exchange resulting from excess deposition of scar tissue. We and others have identified a group of potent polypeptide intracellular messengers, known as growth factors, which are likely to be mediators of the fibroproliferative process in the lung consequent to asbestos inhalation. Thus, we focus on the hypothesis that peptide growth factors such as platelet-derived growth factor, transforming growth factor-beta and tumor necrosis factor-alpha secreted by responding macrophages and epithelial cells are key mediators of the fibroproliferative response. We use a mouse model of IPF in order to investigate the early stages of this disease because most of the pathognomonic histopathologic changes occur within 48 hours of even a brief asbestos exposure. I demonstrate here that compared to C57BL/6 mice, the 129 mouse strain exhibits (1) reduced cell proliferation and growth factor expression at sites of fiber deposition in vivo and (2) failure to develop fibrogenic lesions at these same sites in the lung. I further demonstrate that (3) primary mouse lung fibroblasts (MLFs) isolated from 129 mice exhibit reduced proliferative capacity in vitro in both serum and in serum free defined media containing PDGF when compared to primary MLFs from C57BL/6 mice and (4) that the MLFs isolated from the 129 inbred strain exhibit a reduced responsiveness to factors which upregulate expression of mRNA for procollagen. These findings support the postulate that these peptide growth factors contribute to fibroproliferative lung disease consequent to injury / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_26617 |
| Date | January 1998 |
| Contributors | Brass, David Michael (Author), Brody, Arnold R (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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