Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Generation of superoxide may be a key step in the cytotoxicity mediated by tumour necrosis factor (TNF); cells that cannot produce oxygen radicals might be resistant to TNF. Myeloid haemopoietic cells from patients with chronic granulomatous disease (CGD) cannot produce a large burst of oxygen radicals; therefore we examined the ability of TNF to inhibit clonal growth of myeloid haemopoietic cells from patients and carriers with several types of CGD. Mononuclear light-density cells from the peripheral blood of 13 CGD patients (11 patients with defects of gp91-phox and two with p47-phox), five gp91-phox carriers and 10 normal volunteers were cultured with the appropriate growth factor and TNF in methylcellulose. As expected, TNF (0.001-100 ng/ml) inhibited colony formation of myeloid cells of normal volunteers in a dose-dependent manner. In contrast, clonal growth of myeloid cells of CGD patients was resistant to inhibition by TNF < or = 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which are not capable of producing an oxygen burst, and the action of TGF-beta on clonal growth of myeloid cells, were similar in both the individuals with CGD and the normal volunteers. In X chromosome-linked female carriers of CGD (gp91-phox deficiency), TNF showed an intermediate cytotoxicity on clonal growth of myeloid cells, and analysis of NBT reduction demonstrated that the colonies derived from myeloid cells deficient in gp91-phox were resistant to TNF and those derived from the myeloid cells expressing gp91-phox were inhibited in their proliferation by TNF. This study shows for the first time that myeloid haemopoietic cells from patients with CGD are relatively resistant to the growth-inhibiting effects of high concentrations of TNF.
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PMID:Myeloid haemopoietic cells of patients with chronic granulomatous disease are relatively resistant to TNF. 780 54

With promonocytic leukemia cell line THP-1 cells as an experimental material, the present paper described the proliferation, differentiation and maturation of these cells into m phi-like cells when they were treated with rhTGF-beta 1. Both cell number count and 3H-TdR uptake experiments indicated that rhTGF-beta 1 obviously inhibited the proliferation of THP-1 cells, and the inhibiting effect was related to its concentration. At the same time, the changes in the mode of cell growth and morphology occurred. The cells changed gradually from suspensive into adherent state and formed two groups of cell populations. The number of adherent cells formed was dependent on the concentration and duration of the treatment of rhTGF-beta 1. Therefore, based on the degree of inhibition of cell proliferation and the number of adherent cells with different rhTGF-beta 1 concentrations in a trial experiment, 1.25 ng/ml rhTGF-beta 1 was chosen as the dose in other experiments. From scanning electronmicroscopic observation, it was found that the external morphology of rhTGF-beta 1 treated THP-1 cells gradually transformed into typical macrophage-like cells. Concomitantly, their subcellular organelles also became progressively matured, with primary lysosomes typical for early M phi in 72 h and secondary lysosomes and phagosomes for mature M phi in 120 h of induction, as observed with transmission electron microscope. The ANAE activity, NBT reduction and phagocytosis of differentiated adherent cells were higher than those of control cells and suspensive cells. Specific anti-human TGF-beta-neutralizing mAb could completely block the differentiation of THP-1 cells into M phi-like cells. To sum up, from the results of the studies on cell morphology, growth mode, ultrastructures, phagocytosis, enzyme activation and TGF-beta 1 mAb blocking of induction and differentiation, it is clear that rhTGF-beta 1 can induce THP-1 cells to differentiate and mature into M phi-like cells, with the parallel development of cytoplasmic organoids, phenotype variation and the gaining of phagocytosis activity etc. Concordantly, rhTGF-beta 1 made the M phi-like cells to an activated state as they became matured during the induced differentiation.
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PMID:[rhTGF-beta 1 induced differentiation of human promonocytic leukemia THP-1 cells]. 977 81