Fibroblast proliferation factors in pulmonary granuloma induced by Trichosporon cutaneum in rabbits: presence of a lymphocyte-derived fibroblast proliferation factor and its functional specificity.

Abstract

The fibroblast proliferation activity (FPA) in pulmonary granulomatous lesions in rabbits which were exposed once (primary response) or twice (secondary response) to Trichosporon cutaneum was examined using R9ab, a rabbit fibroblast cell line cell, and fibroblasts from the lesions of the primary and secondary responses. The FPA in lung extracts and cell-free culture supernatants of bronchoalveolar lavage cells from the secondary response was more evident than that from the primary response. FPA from the primary response were recovered at about 60, 18, and 4.5 kD and those from secondary response at about 60, 26, 18, and 4.5 kD on Sephadex G-75 gel filtration. Among the FPA, the activity with a molecular weight of 26 kD and a pI of 7.0 was derived from lymphocytes, whereas the other activities were derived from macrophages. The macrophage-derived fibroblast proliferation factors (FPF) enhanced proliferation of fibroblasts from the lesions of both primary and secondary responses, while the lymphocyte-derived FPF enhanced only proliferation from the secondary response. It was further found that lymphocyte-derived FPF could chemotactically attract fibroblasts from the secondary but not the primary response, indicating functional specificity of lymphocyte-derived FPF on fibroblasts in the secondary response. The present results suggest that this lymphokine with fibroblast proliferation and chemotactic activity plays an important role in the granuloma formation in the secondary response to T. cutaneum.