Effects of purified macrophage RNases on granuloma fibroblasts with reference to silicosis

Abstract

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.

Chronic Exposure to Glucocorticoids Shapes Gene Expression and Modulates Innate and Adaptive Activation Pathways in Macrophages with Distinct Changes in Leukocyte Attraction

“…We matured human peripheral monocytes of five donors into macrophages for 7 d in the presence of FP, which has the longest GC half-life in vitro (7). At day 7, we conducted whole genome analysis using microarrays covering 31,000 annotated genes and found 165 unique genes significantly regulated by FP (Table I, Supplemental Table I) (26)(27)(28)(29)(30)(31). Among the genes most upregulated by FP were GLDN (gliomedin), RNASE1 (RNase 1), and ADORA3 (adenosine A3 receptor), the latter was also upregulated in monocytes (Table II) (19), whereas CCL22, FCN1 (ficolin), and MMP7 were the most downregulated.…”

“…Although ficolin can recognize common carbohydrate residues found in microbes (26), a role for gliomedin in macrophages is not described. Secreted RNase 1 is able to regulate the metabolism of granulation tissue fibroblasts by increasing RNA degradation, affecting metabolic state (27), which can also have consequences for the plasticity of the macrophage response. ADORA3 also is one of the most strongly upregulated genes in smoking-dependent reprogramming of alveolar macrophages in COPD (28).…”