Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM-CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo.
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PMID:Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients. 246 38

Recombinant interleukin (IL) 1 beta and tumor necrosis factor/cachectin (TNF-alpha) induce, usually within 2 h, a dose-dependent increase in the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and G-CSF mRNA in cultured human fibroblasts. Maximal induction is reached at about 4-8 h and usually last for at least 48 h. IL 1 beta and TNF have additive effects on the levels of GM- and G-CSF mRNA, and on the secretion of G-CSF activity into the culture medium. IL 1 alpha has the same additive effect that IL 1 beta has with TNF, but no additive effect with IL 1 beta. In contrast, the high basic level of M-CSF (CSF-1) mRNA shows little or lower variations in response to IL 1, TNF-alpha or both IL 1 and TNF-alpha also induce, with similar kinetics, an increase in IL 1 beta but not mRNA level. In contrast to what is observed with macrophages and endothelial cells, E. coli lipopolysaccharide does not modify the fibroblast CSF mRNA level up to 48 h of culture.
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PMID:Interleukin 1 and tumor necrosis factor-alpha additively increase the levels of granulocyte-macrophage and granulocyte colony-stimulating factor (CSF) mRNA in human fibroblasts. 246 2

Exogenous interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) (type I IFNs) are known to suppress the IFN-gamma-dependent expression of class II MHC (Ia) antigens on macrophages (M phi). We report here that the endogenous type I IFNs produced by M phi in response to IFN inducers regulate Ia expression of the M phi themselves. Coculture of M phi with IFN-gamma and polyinosinic-polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression in comparison with those cultured without poly(I):poly(C). Pretreatment of M phi with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a potent IFN inducer, in vitro or in vivo, before being exposed to IFN-gamma was also effective in suppressing the Ia expression. Such suppression was abolished by the addition of anti-IFN-alpha/beta antibodies to the M phi culture along with IFN-gamma. M phi cultured with L-cell conditioned medium (LCM) containing M-CSF were less capable of expressing Ia antigens than those cultured without LCM. The Ia-expressing ability of LCM-treated M phi was also restored by the addition of anti-IFN-alpha/beta antibodies. M phi in the early stage of sterile inflammation were less responsive to IFN-gamma than those in the late stage. These results suggest that endogenous type I IFNs, which are produced in response to natural or synthetic IFN-inducers, regulate M phi Ia expression in an autocrinal manner.
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PMID:Suppression of macrophage Ia antigen expression by endogenous interferon-alpha/beta. 250 82

Bone marrow-derived macrophages were used to study the mechanism of action of recombinant gamma interferon associated with multilamellar phospholipid liposomes. Gamma interferon associated with liposomes caused an inhibition of [3H]-thymidine uptake induced by macrophage colony-stimulating factor (CSF-1), and primed macrophages for subsequent induction of tumoricidal activity by bacterial lipopolysaccharide (LPS). The liposomes were equally active whether the gamma interferon was added before, or after vesicle formation. The result suggested that significant biologically active gamma interferon was bound to the outside of the vesicles. Interferon binding to liposomes was confirmed using radiolabelled ligand. The liposomes themselves were found to be biologically active in promoting proliferation and in acting synergistically to prime cytotoxicity. Vesicles that contained both phosphatidylethanolamine and phosphatidyl-serine or succinylated phosphatidylethanolamine were most active. Such vesicles were found to be internalised rapidly by bone marrow-derived macrophages. Thus, encapsulation of ligand, and internalisation into cytoplasm, do not appear to be involved in the action of liposome-associated gamma interferon. On the other hand, the liposomes may contribute in other ways to improving the therapeutic potential of gamma interferon.
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PMID:Encapsulation is not involved in the activities of recombinant gamma interferon associated with multilamellar phospholipid liposomes on murine bone marrow-derived macrophages. 250 21

Bone marrow-derived murine macrophages were used to study the relationship between the proliferative response of macrophages to macrophage colony-stimulating factor (CSF-1) and their activation for cytocidal activity against tumour cells. Macrophage activation required two sequential signals. Lymphokines (gamma interferon, interleukin-4) provided the first (priming) signal; bacterial products (lipopolysaccharide, lipophilic muramyl tripeptide, lipopeptide 31362, pertussis toxin) provided the second (triggering) signal. Both priming and triggering agents inhibited [3H]-thymidine uptake by macrophages stimulated with CSF-1. The antiproliferative activity of priming and triggering stimuli was synergistic. Pretreatment with triggering stimuli at 37 degrees C caused a rapid reduction of the subsequent binding of [125I]-CSF-1 to the cell surface at 4 degrees C, whereas priming agents had relatively little effect. Growth inhibition by both priming and triggering agents was largely reversible by washing the cells, and occurred even when they were added as long as 24 h after the growth factor. The ability of pertussis toxin to both inhibit CSF-1-induced proliferation and trigger cytotoxicity in macrophages suggests the involvement of a regulatory GTP-binding protein (G protein) in both processes.
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PMID:Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony-stimulating factor (CSF-1): involvement of a pertussis toxin-sensitive reaction. 254 52

Nonadherent cells of the bone marrow of C3H/HeN mice were incubated for 3 days with the culture supernatant of an L-929 cell line containing macrophage-colony-stimulating factor. Approximately, 70% of the cells became phagocytic, adherent to plastic dishes and positive for nonspecific esterase staining. The adherent cells exhibited a weak tumoricidal activity against syngeneic mammary carcinoma cells, and the cytotoxicity was strongly augmented by the addition of bacterial lipopolysaccharide to the cytotoxicity assay. The cytotoxicity induced by lipopolysaccharide was also shown to be mediated by Thy1.2- and asialo-GM1+ cells, and was abrogated by the addition of carrageenan. Macrophage-colony-stimulating-factor-producing (D66) and nonproducing (A23) variants were separated from the MM48 tumor line in in vitro culture following limiting dilution. There was no difference between these two variants in either the in vitro growth rate or the susceptibility to macrophage-mediated cytotoxicity. C3H/HeN mice inoculated i.p. with D66 survived longer than did those inoculated i.p. with A23. C3H/HeN mice bearing D66 or A23 as an ascitic form were given i.p. injections of Nocardia rubra cell wall skeleton (N-CWS). N-CWS significantly prolonged the survival period of mice bearing D66, whereas it exhibited no apparent antitumor effect on mice bearing A23. The increase in the cell number of D66 in the peritoneal cavity was significantly retarded, compared with that of A23. In contrast, the number of peritoneal macrophages increased more in D66-bearing mice than in A23-bearing mice. The increase in the peritoneal macrophage number was further augmented by an i.p. injection of N-CWS. Peritoneal macrophages of D66-bearing mice exhibited apparent tumoricidal activity against MM48 tumor cells in the presence of lipopolysaccharide, and the cytotoxicity was significantly augmented by i.p. injection of N-CWS. On the other hand, the responsiveness of peritoneal macrophages to lipopolysaccharide was found to be poor in A23-bearing mice and the tumoricidal activity was only weakly augmented by N-CWS. These results strongly suggest that M-CSF plays an important role not only in the maturation of macrophage progenitors but also in the induction and the accumulation of activated macrophages.
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PMID:Induction of tumoricidal macrophages from bone marrow cells of normal mice or mice bearing a colony-stimulating-factor-producing tumor. 264 51

Human alveolar macrophages (AMO) have been investigated for their ability to produce three monokines, tumor necrosis factor-alpha (TNF), macrophage colony stimulating factor (CSF-1), and interleukin 1-beta (IL-1). No TNF activity was found in supernatants of unstimulated AMO cultured for 20 h, although TNF mRNA was detected in the cells by Northern blot analysis. Stimulation of the cells with lipopolysaccharide (LPS) induced production and release of high levels of TNF into the culture supernatant. Increased levels of TNF mRNA were detectable at 90 min after LPS stimulation by dot blot analysis, reaching maximum expression between 4 and 8 h and declining thereafter. TNF activity peaked at approximately 8 h in the AMO supernatants. After 24 h TNF production had ended. Compared to autologous monocytes the AMO produced 5.7 times more TNF on a per cell basis (activity accumulated in 20 h supernatants). Uncultured AMO expressed CSF-1 mRNA which was translated into active protein recovered in supernatants upon culture in the absence of stimulus. The addition of LPS to AMO slightly reduced both mRNA levels and amount of factor in the supernatants. In contrast to the AMO, monocyte production of CSF-1 was enhanced by LPS. CSF-1 production by AMO continued for at least 48 h of culture. Spontaneous production of low amounts of IL-1 was found in one-third of the AMO samples, while low levels of IL-1 mRNA were present in all tested preparations. LPS stimulation induced increase in IL-1 mRNA within 90 min; mRNA levels peaked between 12 and 20 h and stayed high for at least 42 h. However, while all LPS-stimulated AMO expressed high levels of IL-1 mRNA biologically active IL-1 was again detected only in a fraction of the AMO supernatants. These results show that the production of monokines CSF-1, TNF, and IL-1 is differentially regulated by LPS in alveolar macrophages and has different responses as compared to monocytes. The longevity of the messages for each of the factors is possible indicators of the relative contribution of these factors to the response to endotoxin-induced injury and repair processes in the lung.
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PMID:Differential production of tumor necrosis factor, macrophage colony stimulating factor, and interleukin 1 by human alveolar macrophages. 264 30

Lipoprotein from the outer membrane of Escherichia coli and the synthetically prepared lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 derived from the N-terminus of lipoprotein constitute potent macrophage and polyclonal B-lymphocyte activators. The compounds have also been shown to induce tumor cytotoxicity in murine bone marrow-derived macrophages (BMDM). Bone marrow stem cells were cultured in the presence of colony-stimulating factor 1 to yield BMDM of 98 to 99% purity at day 8. After stimulation with the lipopeptides on days 4, 6, 8 and 10 of bone marrow culture, the cytotoxic effect of BMDM on the tumor cell line L929 was determined in a [3H]thymidine release assay. Maximum tumor cytotoxicity was found on day 8 with an optimal effector/target-cell ratio of 10:1, and a duration of lipopeptide stimulation of 4 h. The supernatants of lipopeptide stimulated BMDM also showed cytotoxic activity that could be inhibited by antiserum against tumor necrosis factor alpha. The effects of the lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 were comparable or superior to those exerted by lipopolysaccharide. Our results demonstrate that synthetic lipopeptides are potent activators for murine BMDM and may therefore prove to be an important tool for the elucidation of the role of macrophages in the host defence mechanisms against tumor cells.
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PMID:Induction of tumor cytotoxicity in murine bone marrow-derived macrophages by two synthetic lipopeptide analogues. 277 84

We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony-stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G-CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.
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PMID:Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro. 278 82

The role of mononuclear phagocyte-specific colony-stimulating factor (CSF-1) in human monocyte to macrophage differentiation was investigated. The addition of 1000 U/ml of CSF-1 to serum-free monocyte cultures resulted in monocyte survival comparable to that in cultures containing 5% AB serum, whereas cells in serum- and CSF-1-free medium lost their viability in 3 to 5 days. The requirement for CSF-1 coincided with the time (40 to 64 hr of culture) when the major changes in morphology and biochemical function took place in monocytes undergoing differentiation into macrophages. If CSF-1 was removed from the cultures before this time, death of the monocytes resulted. In cultures containing CSF-1, as in serum containing cultures, the lysosomal enzyme acid phosphatase was enhanced 10- to 20-fold by day 4 to 5. Superoxide production in response to phorbol myristic acetate was maintained in CSF-1 cultured monocytes, but declined with time in monocytes cultured in serum. The expression of monocyte-macrophage antigens p150.95 (LeuM5), OKM1, LeuM3, Fc receptors (32.2), and HLA-DR had increased in CSF-1 containing cultures at day 4. When antigen expression was analyzed at day 2 to 3, when cell size and 90 degrees scatter characteristics were still identical to control serum-free cultures, only p150.95, HLA-DR and FcR expression were enhanced by CSF-1. Low amounts of lipopolysaccharide (0.1 ng/ml) were found to enhance monocyte survival in the absence of added CSF-1. Lipopolysaccharide-containing cultures were found to produce CSF-1 (up to 450 U/ml, as detected by radioimmunoassay). Lipopolysaccharide (1 microgram/ml), however, did not induce enhanced expression of the maturation-related antigens. Based on these observations we conclude that CSF-1 is enhancing human monocyte survival and is involved in the events leading to the differentiation of monocytes into macrophages.
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PMID:Colony-stimulating factor-induced monocyte survival and differentiation into macrophages in serum-free cultures. 282 12


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