RAPID ACTIVATION OF PDGF-A AND PDGF-B EXPRESSION AT SITES OF LUNG INJURY IN ASBESTOS-EXPOSED RATS

The development of interstitial pulmonary fibrosis is associated with a variety of inflammatory mediators, including peptide growth factors and cytokines. In the work presented here, we have asked whether or no t platelet-derived growth factor (PDGF)-A and -B genes and proteins ar e expressed in anatomic and temporal patterns consistent with this fac tor playing a role in the disease process. Using an established rat mo del of asbestos-induced fibroproliferative lung disease, we demonstrat e elevated levels of PDGF-A and -B mRNAs in total lung RNA immediately after a single 5-h exposure to similar to 1,000 fibers/ml of chrysoti le asbestos. In situ hybridization revealed the PDGF-A and -B in RNAs primarily in macrophages and bronchiolar-alveolar epithelial cells at sites of initial fiber deposition and lung injury. There was clear evi dence of PDGF-A and -B mRNAs in interstitial cells as well. The patter n of in situ hybridization was entirely consistent with the appearance (established by immunohistochemistry) of PDGF-A and -B proteins by 24 h post-exposure in the same cell types. Both mRNAs and proteins remai ned detectable at the fiber deposition sites for almost 2 wk post-expo sures. These findings are consistent with our previous studies showing increased mesenchymal cell proliferation and fibroproliferative lesio ns that progress at the sites where PDGF-A and -B are expressed. Altho ugh it is clear that multiple growth factors are produced simultaneous ly at sites of initial injury, we suggest that the PDGF isoforms could be playing a central role in the disease process based upon their pot ent mitogenic effects upon mesenchymal cells.