Persistent pulmonary interstitial fibrosis, induced by immune response to TNP, is associated with altered mRNA procollagen type I:III ratio.

Pulmonary interstitial fibrosis is characterized by a progressive increase in connective tissue in the lung parenchyma. Fibrosis is associated with conditions that result as a consequence of cell mediated responses including graft versus host disease, delayed type hypersensitivity reactions, and granulomas. The hapten-immune animal model for pulmonary interstitial fibrosis correlates the nonresolving fibrosis observed in the lung parenchyma directly with the animal's prior immunization to the hapten. Because the model is patterned after the well studied contact hypersensitivity assay in the skin, the immune response can be directly correlated with a cell-mediated (T-lymphocyte) immune mechanism. Previously, we reported that hapten-immune animals showed increased collagen deposition as identified on routine paraffin fixed slides that were stained with Masson's trichome. In this report, morphometric procedures were used to quantitate the fibrotic lesion. Fibroblasts were harvested from lungs of all treatment groups, cultured, and assayed for collagen production. Once it was determined that collagen production by fibroblasts was similar to that recorded in assays using fresh lung tissue, the fibroblasts were used as a homogeneous cell source for RNA. Total RNA from various treatment groups was used to assess the ratio of mRNA for procollagen I:III using slot and northern blot hybridization procedures. An increased ratio in the procollagen type I:III mRNA was observed in total RNA isolated from fibroblasts from immune and challenged hamsters, and not in samples from all other groups. These results support the hypothesis that the activated T lymphocytes involved in "contact" hypersensitivity-like reactions in the lung regulate not only the quantity, but also the quality of collagen produced by the fibroblasts in the lungs of the hamsters that develop nonresolving fibrosis. The model may be important for the study of skin and pulmonary disease induced by exposure to environmental haptens.