An agent in rheumatoid synovial fluid which stimulates collagen synthesis by embryonic chick tendon cells was identified as glutamine. The stimulating effect was observed only at a subnormal concentration of proline (0.02 mM). The concentration of glutamine in rheumatoid synovial fluid is about 2.5 mM but it falls rapidly during storage even at -20 degrees C. Collagen synthesis is shown to depend on the extracellular concentrations of glutamine and proline in addition to any connective tissue activating factors.
A hypothesis is presented for the action of silica-treated macrophages on protein synthesis in fibroblasts and also a method for the isolation of silica-attached materials in lung tissue. The increased protein synthesis in the fibroblasts is due, at least partly, to an increase in mRNA. Silica prevents the suppressing "macrophage effect" of macrophage-originated ribonuclease on fibroblasts. However, under certain conditions, collagen synthesis is stimulated by silica-treated macrophage preparations to such an extent that the effect cannot be explained by the inhibition of macrophage ribonuclease alone. We therefore postulate the existence of a fibrogenic factor, which is released by the macrophages. This factor has been demonstrated and can be purified from lung homogenate of SiO2-treated rats.ImagesFIGURE 2.FIGURE 5.FIGURE 6. (a)FIGURE 6. (b)
Two alkaline RNases, designated RNase 1 and RNase 2, were isolated from the culture media of silica-treated and non-treated macrophages. The yield of RNase from the medium of silica-treated macrophages was 30% of that from the non-treated control. The effects of these RNases on cultured granuloma fibroblasts and on granulation-tissue nuclei were studied. RNase 1 inhibited thymidine incorporation into fibroblasts except at low concentrations, where it was observed to be stimulatory. RNase 1 also inhibited the protein synthesis of fibroblasts. The incorporation of cytidine into RNA in cultured fibroblasts was not affected by RNase 1, but the incorporation into isolated nuclei was decreased. In pulse chase experiments RNase 1 increased the release of cytidine, but not that of thymidine, from the cells. RNase 2 had no effect on the protein or nucleic acid metabolism of the fibroblasts or on the RNA metabolism of isolated nuclei, perhaps because of impermeability. These experiments confirm that macrophage RNase activity is able to regulate the metabolism of granulation-tissue fibroblasts by increasing RNA degradation. Through this action it also regulates DNA and protein synthesis and other metabolic functions of those cells.
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