In this study microglial cells isolated from brain cell cultures of newborn mice were characterized and investigated for morphology, their responses to growth factors and their functional properties. The microglial cells were phagocytic, contained nonspecific esterase activity and expressed Fc (IgG1/2b) and type-3 complement receptors. Scanning electron microscopy revealed that in analogy to brain tissue two types of microglial cells are present in the cultures: the ameboid and the ramified type which both display similar appearance by transmission electron microscopy. Interleukin 3 and the granulocyte-macrophage colony-stimulating factor were potent growth factors for the cultured microglial cells. The cells were negative for class II antigens (Ia) of the major histocompatibility antigen complex. However, upon treatment with interferon-gamma (IFN-gamma) microglial cells became Ia+ and functioned as antigen-presenting cells when tested on ovalbumin-specific Ia-restricted helper T cells. Furthermore, microglial cells exposed to IFN-gamma and endotoxin developed tumor cell cytotoxicity and produced tumor necrosis factor alpha. Taken together, microglial cells share the characteristics of cells of the macrophage lineage.
Biogenic amines, e.g. histamine, occur in many different foods. At high concentrations, they are risk factors for food intoxication, whereas moderate levels may lead to food intolerance. Sensitive persons, with insufficient diamine oxidase activity, suffer from numerous undesirable reactions after intake of histamine containing foods. Besides spoiled foodstuffs, especially fermented foods tend to contain elevated levels of biogenic amines, although their concentrations vary extensively not only between different food varieties but also within the varieties themselves. High histamine content in foods and beverages result from microbial contamination. The evidence of enteral histaminosis represents a challenge for the food industry to produce foods with histamine levels as low as possible. We therefore investigated critical steps for histamine formation during food production processes, and established production methods that include low-histamine technology.
Human glioblastoma cells secrete a peptide, termed glioblastoma‐derived T cell suppressor factor (G‐TsF), which has suppressive effects on interleukin‐2‐dependent T cell growth. As shown here, complementary DNA for G‐TsF reveals that G‐TsF shares 71% amino acid homology with transforming growth factor‐beta (TGF‐beta). In analogy to TGF‐beta it is apparently synthesized as the carboxy‐terminal end of a precursor polypeptide which undergoes proteolytic cleavage to yield the 112 amino‐acid‐long mature form of G‐TsF. Comparison of the amino‐terminal sequence of G‐TsF with that of porcine TGF‐beta 2 and bovine cartilage‐inducing factor B shows complete homology, which indicates that we have cloned the human analogue of these factors. It is tempting to consider a role for G‐TsF in tumor growth where it may enhance tumor cell proliferation in an autocrine way and/or reduce immunosurveillance of tumor development.
T cell suppressor factor produced by human glioblastoma cells inhibits T cell proliferation in vitro and more specifically interferes with interleukin-2 (IL-2)-dependent T cell growth.Here we report the purification of this factor from conditioned medium of the human glioblastoma cell line 308. Aminoterminal sequence analysis of the 12.5-kd protein demonstrates that eight out of the first 20 amino acids are identical to human transforming growth factor-fl. Purified glioblastoma-derived T cell suppressor factor and transforming growth factor-,B from porcine platelets inhibit both 1L-2-induced proliferation of ovalbumin-specific T helper cells and lectin-induced thymocyte proliferation with similar specific activities. If released by glioblastoma cells in vivo, the factor may contribute to impaired immunosurveillance and to the cellular immunodeficiency state detected in the patients.
Human glioblastoma cells secrete an inhibitory factor termed "glioblastoma-derived T-cell suppressor factor" (G-TsF). A member of the transforming growth factor beta (TGF beta) family, G-TsF is identical to TGF beta 2. The present study investigated the effect of G-TsF/TGF beta 2 on the proliferative and cytotoxic properties of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). The results demonstrate that the IL-2 (5 to 20 U/ml)-dependent proliferative response of glioma-derived TIL's was inhibited 70% to 85% by G-TsF/TGF beta 2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNF alpha) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNF alpha nor interferon gamma was able to reduce the inhibitory effect of TGF beta 2 on TIL proliferation. In addition, TGF beta 2 suppressed 60% to 100% the cytotoxic response of glioma-derived TIL's against several tumor targets, including autologous glioma cells, and the suppressive effect was shown to be reduced by increasing concentrations of IL-2.
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