CYTOKINE-MEDIATED REGULATION OF TRANSFERRIN SYNTHESIS IN MOUSE MACROPHAGES AND HUMAN T-LYMPHOCYTES

Transferrin (Tf) plays an important role during immunologic activation by donating iron to activated lymphocytes. Therefore, synthesis by ly mphomyeloid cells has been investigated. Mouse macrophages and macroph age cell lines synthesized Tf, with levels being markedly increased by gamma-interferon (gamma-IFN) and, to a lesser extent, by interleukin- 1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha). Tf was also produced by phytohemagglutinin-stimulated human T cells a nd two T-cell lines and was increased by IL-2. Even after appropriate activation, none was synthesized by human macrophages or monocytic cel l lines or by mouse T cells, T-cell lines, or thymus cells. In both sp ecies, B-lineage cell lines were negative. Tf was also synthesised by macrophages from congenitally hypotransferrinemic mice and was respons ive to gamma-IFN, but levels were lower than those from normal control s. Synthesis by human and murine hepatoma cells was increased by IL-6 but unaffected by IL-1, TNF alpha, or gamma-IFN. Iron decreased synthe sis by hepatoma cells but had no effect on the lymphomyeloid cells. Tf mRNA levels parallelled protein synthesis, suggesting that regulation was pretranslational. Thus, Tf synthesis by lymphomyeloid cells is re gulated differently from hepatic synthesis, which is consistent with t he suggestion that Tf may act in a paracrine (mouse) or autocrine (hum an) manner on activated lymphocytes. (C) 1995 by The American Society of Hematology.