Modulation of morphology, proliferation and collagen synthesis in fibroblasts by the exudate from hypersensitive granulomatous inflammation in rats.

We examined the effects of the exudate, collected from rats in which hypersensitive granulomatous inflammation was induced by methylated bovine serum albumin, on the function of inflammatory fibroblasts in culture. Addition of the exudate to the fibroblast culture induced changes in fibroblast morphology, identified by staining with antirat prolyl hydroxylase. Phase-contrast microscopy revealed that the exudate-treated fibroblasts became elongated and formed a network. Scanning electron microscopy showed that numerous long pseudopods covered the surface of the fibroblasts. Transmission electron microscopy revealed microfilament bundles with dense zones parallel to the long axis of the cell and nuclei with folds and indentations. Microfilaments were also visible in the elongated pseudopods. These features were consistent with those of myofibroblasts. The exudate also stimulated fibroblast proliferation and collagen synthesis. These findings suggest that the exudate contained certain factors that modulated fibroblast morphology, proliferation, and collagen synthesis. It is possible that putative endogenous factor(s) at the sites of inflammation modulate the development, contraction, and fibrosis of granulation tissue in hypersensitive granulomatous inflammation.