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

Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (greater than 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 1 1b and anti-Leu7 monoclonal antibodies plus complement did not reduce monocyte-mediated lysis of the melanoma targets, demonstrating that contaminating NK cells, if any, were not responsible for the lysis of noncultured melanoma targets by monocytes. In contrast, Leu 1 1b+ NK cells were responsible for the lysis of the melanoma targets by NK-enriched lymphocytes. The addition of recombinant interferon-gamma (rIFN-gamma), but not lipopolysaccharide, into the 51Cr release assay or pretreatment of monocytes with rIFN-gamma significantly increased their cytotoxicity against noncultured solid tumor cells. Monocytes cultured for 3 days with medium alone lost their cytotoxic activity. The addition of rIFN-gamma from the beginning of these cultures prevented the loss of the cytotoxic activity of monocytes. In summary, both unstimulated monocytes and NK-enriched lymphocytes exhibit comparable levels of spontaneous cytotoxicity against fresh solid tumor targets.
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PMID:Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. 311 44

Interleukin-1 (IL-1) exhibits multiple biological properties on various tissues by modulating immunologic, inflammatory, metabolic, and neurologic functions. Considerable attention has focussed on the measurement of IL-1 activity. We reported a simple, sensitive, and specific bioassay for IL-1 using human melanoma A375 subclone which is highly sensitive for the cell growth inhibitory activity of IL-1. This bioassay method is allows detection of as low as 10pg of IL-1 beta/ml or 30pg of IL-1 alpha/ml. Since this A375 subclone cell dose not respond to prostaglandin E2 plant lectins, lipopolysaccharide, and cytokines such as interleukin-2, interleukin-6, tumor necrosis factor, interferon or colony-stimulating factor, it is an extremely useful and rapid method for the measurement of IL-1 activity in a variety of experimental and clinical conditions. The assay method was used in the presence of antisera to IL-1 beta to discriminate two species of IL-1, IL-1 alpha and IL-1 beta, produced in human peripheral mononuclear cells.
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PMID:A simple, sensitive bioassay for the detection of interleukin-1 using human melanoma A375 cell line. 326 84

Paraformaldehyde-fixed lipopolysaccharide (LPS)-activated human monocytes produced significant lysis of the human melanoma cell line A375. The cytotoxic activity was retained following treatment of the fixed monocytes with anti-tumor necrosis factor (anti-TNF) antibodies but was specifically inhibited by a mixture of anti-TNF and anti-interleukin 1 (anti-IL 1) antibodies. A375 cells were also killed by plasma membranes purified from LPS-activated human blood monocytes. This activity was specifically inhibited by anti-IL 1 alpha antibodies, but only partially inhibited by anti-IL 1 beta antibodies. CHAPS detergent-extracted plasma-membrane IL 1 in its soluble form or associated with lyophilized liposomes was also able to kill A375 cells, and this antitumor activity was inhibited by anti-IL 1 antibodies. These results suggest that membrane IL 1, primarily IL 1 alpha, was cytotoxic for the A375 cells. CKS-17, a peptide synthesized with homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, when covalently bound to BSA partially inhibited the IL 1 activities of tumor cell cytotoxicity and T-cell clone proliferation, displayed by purified plasma membranes, detergent-extracted membrane IL 1, or membrane IL 1 associated with liposomes. These findings indicate that cytotoxic membrane IL 1 can be solubilized by detergent, bound to the surface of liposomes, and specifically inhibited by anti-IL 1 antibodies or the immunosuppressive peptide CKS-17.
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PMID:Cytotoxic liposomes: membrane interleukin 1 presented in multilamellar vesicles. 326 70

Homologous human macrophage hybridoma cell lines were obtained by somatic cell fusion between peripheral blood monocyte-derived macrophages and a subclone of the myelomonocytic cell line, U937-F9. The hybridoma cell lines grown in vitro for more than a year were confirmed by manifestations of phagocytosis, adherence, nonspecific esterase, acid phosphatase, chromosome numbers and other cell surface antigens. Cell surface antigens on hybridomas were detected by flow cytometry analysis with monoclonal antibodies. With interclonal differences, a typical phenotype of hybridoma cells was CDw14+, OKM5+, Mac-1+ (equivalent to OKM1 and Mol), OKT9+, HLA-DR- and CD20+. After stimulation with lipopolysaccharide and calcium ionophore A23187, culture supernatants of clones c18A and c29A showed cytotoxic activity against human melanoma A375 Met-Mix and other cell lines which were resistant to the tumor necrosis factor, lymphotoxin and interleukin 1. This cytotoxic factor was found to be distinct from the tumor necrosis factor, lymphotoxin and interleukin 1 using the anti-tumor necrosis factor, anti-lymphotoxin and anti-interleukin 1 antisera.
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PMID:Homologous human macrophage hybridomas that produce a novel cytotoxic factor in their culture supernatants. 328 4

Adult female B6C3F1 mice were gavaged with TBBC in corn oil at doses of 10, 100, or 200 mg/kg daily for 14 consecutive days. All immunological parameters were measured 24 hr after the last chemical exposure. When indicated, animals were immunized during the exposure. TBBC produced a decrease in the peak IgM (44%) and peak IgG (48%) antibody response to sheep erythrocytes (SRBCs), but had no effect on the delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH). Paradoxically, TBBC caused an overall increase in the number of splenic cells, a decrease in the percentage of splenic T cells and no effect on the percentage of splenic B cells. There were no effects on the lymphoproliferative responses to optimal concentrations of concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS), but there was a significant decrease in the mixed lymphocyte response (MLR). In both the mitogen assays and the MLR there was a dose-related increase in the basal (unstimulated) DNA synthesis of the spleen cells. Innate immunity, as measured by natural killer (NK) cell activity and serum complement, was significantly increased. Effects on macrophage function were complex, as an increase or no effect was observed depending on the parameter measured. In the host resistance models, animals were infected with various pathogens 24 hr after the last chemical exposure. Exposure to TBBC caused an increased resistance to challenge with Streptococcus and B16F10 melanoma, a decreased resistance to challenge with PYB6 tumors, and no effect on the resistance to HSV-2, Listeria or Plasmodium.
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PMID:An immunotoxicological evaluation of 4,4'-thiobis-(6-t-butyl-m-cresol) in female B6C3F1 mice. 2. Humoral and cell-mediated immunity, macrophage function, and host resistance. 339 96

Clinical observations suggest that tumors grow more slowly in aged subjects. To investigate the influence of age on tumor growth, we injected the same number of cultured B16 melanoma cells into C57BL/6 mice of various ages. B16 melanoma cells, inoculated s.c., grew more slowly in old (18-20-month-old) as compared to young (6-8-week-old) mice. In young tumor-bearing mice there was a significant increase in the number and the proliferative response to phytohemagglutinin and concanavalin A of splenic T-cells as compared to old tumor-bearing animals. There was no difference in the response of B-lymphocytes from old and young tumor-bearing mice to lipopolysaccharide. The positive association between T-cells and the rate of tumor growth was also suggested by the slower growth of melanoma cells in thymectomized or thymectomized and anti-theta antiserum-treated young mice. Finally, the age-associated difference in tumor growth could be transferred by spleen cells from old or young mice to thymectomized and lethally irradiated syngeneic young animals. Young mice with rapidly growing B16 melanoma tumors have increased numbers and proliferative responses of thymic-derived lymphocytes. It is likely that T-cells or their products facilitate the growth of B16 tumor cells.
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PMID:Role of the thymus and T-cells in slow growth of B16 melanoma in old mice. 349 26

We investigated the in vitro activation of rat liver macrophages to a tumoricidal state with free and liposome-encapsulated immunomodulators. The cytolytic activity of liver macrophages was determined by a radioactivity release assay using murine B16 melanoma cells, labeled with [methyl-3H]thymidine. Exposure of the liver macrophages to concentrations of 50 micrograms of free, nonencapsulated, muramyl dipeptide (MDP) per ml resulted in maximal levels of tumor cell lysis of approximately 20%. Encapsulation of the MDP within liposomes (multilamellar vesicles, 0.3 to 0.5 micron in diameter, consisting of egg phosphatidylcholine, cholesterol, and dicetylphosphate, 4:5:1) not only caused a 500-fold reduction in the amount of MDP required to obtain the same levels of cytolysis but also increased the maximally obtainable level of cytolysis more than 2-fold. A synergistic effect of lipopolysaccharide and free or encapsulated MDP on cytolytic activity was observed when the macrophages were exposed to a combination of the two agents simultaneously. Besides causing tumor cell lysis, activated macrophages were also able to suppress tumor cell proliferation by 80 to 90% as determined by a [methyl-3H]thymidine incorporation assay. With a fixed amount of MDP, encapsulated in different amounts of liposomal lipid, the extent of macrophage activation was found to increase with a larger amount of encapsulating lipid. This increase in macrophage activation may be the result of a sustained intracellular release of encapsulated MDP from the liposomes. Liposome structure and composition will thus be important parameters in the in vivo application of liposomes as carriers of immunoactive substances.
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PMID:In vitro activation of rat liver macrophages to tumoricidal activity by free or liposome-encapsulated muramyl dipeptide. 373 Oct 91

Human monocytes obtained from healthy volunteers and isolated by centrifugal elutriation were not cytotoxic to allogeneic tumorigenic cells. These freshly isolated monocytes were rendered tumoricidal following interaction in vitro for 24 hours with greater than 0.01 micrograms lipopolysaccharide (LPS)/ml or over 1 microgram nor-muramyl dipeptide/ml. Monocytes activated by this procedure produced a soluble factor that lysed tumor cells. Full expression of tumor cell lysis required a minimum of 18 hours' exposure of tumor cells to the factor. The degree of tumor cytotoxic factor (TCF) production was closely related to the intensity of monocyte activation to become tumoricidal. Significant production of TCF by monocytes was detected in the supernatants after treatment for 3 hours with LPS. TCF was also released by activated monocytes when cocultivated with tumorigenic cells. Similarly, the level of TCF production correlated with the monocyte density. TCF destroyed human allogeneic tumor cell lines (melanoma, glioblastoma, colon carcinoma, prostatic carcinoma, and breast carcinoma), but it did not affect nontumorigenic cell lines (lung and skin fibroblasts). TCF activity was not blocked by superoxide dismutase, catalase, or protease inhibitors; it was destroyed by being heated at 100 degrees C for 2 minutes. The ability of activated monocytes to release TCF could enhance host defense against cancer.
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PMID:Kinetics and function of tumor cytotoxic factor(s) produced by human blood monocytes activated to the tumoricidal state. 385 62

Phorbol myristate acetate (PMA), the most potent of the tumor promoting phorbol diesters, modulates function in several immunoresponsive cells following in vitro exposure. Since suppression of cellular mechanisms capable of limiting tumors and infections can adversely affect health, these experiments were designed to evaluate relevant components of cell-mediated immunity (CMI) following in vivo PMA exposure, and to determine the biological significance of any alterations utilizing assays of host resistance. Adult, female B6C3F1 mice were administered 0.2, 2.0, 20.0 or 40.0 micrograms PMA/g body weight subcutaneously over a two-week period. Mechanisms of cell-mediated host resistance were assessed by quantitating natural killer (NK), cytotoxic T-lymphocyte (CTL) and macrophage-mediated lysis of radiolabelled tumor target cells, and macrophage-induced cytostasis in tumor cell populations. Macrophages from PMA-treated mice were cytostatic to tumor cells, inhibiting up to 90% of growth in cultured tumor cells, but were not tumoricidal. Furthermore, pyran-elicited (primed) macrophages, which are activated to fully cytotoxic states by in vitro exposure to lipopolysaccharide, were inhibited in tumoricidal activation by in vivo PMA exposure. The induction of responsive but not cytotoxic macrophages by in vivo PMA exposure is consistent with the enhanced resistance to Listeria bacterial challenge, and increased susceptibility to B16F10 tumor and Trichinella parasitic challenges observed in these mice. Furthermore, previous reports of decreased in vitro NK activity following in vivo PMA exposure and present observations of correlative decreases of in vivo NK activity (55% decrease in mice exposed to 20 micrograms PMA/g) suggest an important role for NK activity in limiting in vivo B16F10 melanoma growth. CTL effector function was less susceptible to PMA-induced suppression than NK function at similar dosages, further supporting a predominant role of macrophages and NK cells or possibly other effector functions in the resistance to Listeria, Trichinella, or B16F10 challenge. Nevertheless, significant suppressive effects of PMA on CTL function at higher dosages cannot be excluded as contributing to altered host resistance to these agents. These studies demonstrate that in vivo exposure to PMA can modify cell-mediated mechanisms of host resistance with coincident alterations in the incidence of infections and tumors.
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PMID:Correlation of murine susceptibility to tumor, parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the tumor promoter phorbol myristate acetate. 387 95

Murine peritoneal macrophages elicited by dimethyldioctadecylammonium bromide (DDA), which is a potent immunologic adjuvant, were examined for cytotoxic and growth inhibiting activity for malignant cells. DDA macrophages had no cytolytic activity for murine B16BL-6 melanoma or human SMS-SB pre-B leukemia cells even in the presence of up to 1 microgram bacterial endotoxin (lipopolysaccharide, LPS)/ml. However, they exhibited a variable inhibitory effect on the growth of several lines of leukemia cells. The number of SMS-SB and human NALL cells remained essentially static in the presence of DDA macrophages while they increased significantly when cultured with resident macrophages. In contrast, L1210 cells increased 5-8-fold in the presence of macrophages elicited either by DDA or the inflammatory agent proteose peptone (PP). Although DDA macrophages retarded L1210 growth relative to PP macrophages, both populations responded to LPS in a comparable dose dependent manner to become essentially cytostatic at 1 microgram LPS/ml.
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PMID:Effect of dimethyldioctadecylammonium bromide induced macrophages on malignant cell proliferation. 400 32


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