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)

Tuberculosis remains one of the major infectious causes of morbidity and mortality in the world, yet the mechanisms by which macrophages defend against Mycobacterium tuberculosis have remained obscure. Results from this study show that murine macrophages, activated by interferon gamma, and lipopolysaccharide or tumor necrosis factor alpha, both growth inhibit and kill M. tuberculosis. This antimycobacterial effect, demonstrable both in murine macrophage cell lines and in peritoneal macrophages of BALB/c mice, is independent of the macrophage capacity to generate reactive oxygen intermediates (ROI). Both the ROI-deficient murine macrophage cell line D9, and its ROI-generating, parental line J774.16, expressed comparable antimycobacterial activity upon activation. In addition, the oxygen radical scavengers superoxide dismutase (SOD), catalase, mannitol, and diazabicyclooctane had no effect on the antimycobacterial activity of macrophages. These findings, together with the results showing the relative resistance of M. tuberculosis to enzymatically generated H2O2, suggest that ROI are unlikely to be significantly involved in killing M. tuberculosis. In contrast, the antimycobacterial activity of these macrophages strongly correlates with the induction of the L-arginine-dependent generation of reactive nitrogen intermediates (RNI). The effector molecule(s) that could participate in mediating this antimycobacterial function are toxic RNI, including NO, NO2, and HNO2, as demonstrated by the mycobacteriocidal effect of acidified NO2. The oxygen radical scavenger SOD adventitiously perturbs RNI production, and cannot be used to discriminate between cytocidal mechanisms involving ROI and RNI. Overall, our results provide support for the view that the L-arginine-dependent production of RNI is the principal effector mechanism in activated murine macrophages responsible for killing and growth inhibiting virulent M. tuberculosis.
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PMID:Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. 155 82

Quantification of intracellular and extracellular levels and production rates of reactive oxygen species is crucial to understanding their contribution to tissue pathophysiology. We measured basal rates of oxidant production and the activity of xanthine oxidase, proposed to be a key source of O2- and H2O2, in endothelial cells. Then we examined the influence of tumor necrosis factor-alpha and lipopolysaccharide on endothelial cell oxidant metabolism, in response to the proposal that these inflammatory mediators initiate vascular injury in part by stimulating endothelial xanthine oxidase-mediated production of O2- and H2O2. We determined a basal intracellular H2O2 concentration of 32.8 +/- 10.7 pM in cultured bovine aortic endothelial cells by kinetic analysis of aminotriazole-mediated inactivation of endogenous catalase. Catalase activity was 5.72 +/- 1.61 U/mg cell protein and glutathione peroxidase activity was much lower, 8.13 +/- 3.79 mU/mg protein. Only 0.48 +/- 0.18% of total glucose metabolism occurred via the pentose phosphate pathway. The rate of extracellular H2O2 release was 75 +/- 12 pmol.min-1.mg cell protein-1. Intracellular xanthine dehydrogenase/oxidase activity determined by pterin oxidation was 2.32 +/- 0.75 microU/mg with 47.1 +/- 11.7% in the oxidase form. Intracellular purine levels of 1.19 +/- 1.04 nmol hypoxanthine/mg protein, 0.13 +/- 0.17 nmol xanthine/mg protein, and undetectable uric acid were consistent with a low activity of xanthine dehydrogenase/oxidase. Exposure of endothelial cells to 1000 U/ml tumor necrosis factor (TNF) or 1 microgram/ml lipopolysaccharide (LPS) for 1-12 h did not alter basal endothelial cell oxidant production or xanthine dehydrogenase/oxidase activity. These results do not support a casual role for H2O2 in the direct endothelial toxicity of TNF and LPS.
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PMID:Responses of vascular endothelial oxidant metabolism to lipopolysaccharide and tumor necrosis factor-alpha. 156 24

The role of macrophage activation in the killing of L. monocytogenes is unclear. Some studies suggest that activation for enhanced production of reactive oxygen and nitrogen intermediates may not be of central importance. Recent data have indicated an important role for interferon-gamma (IFN-gamma) induced retention of L. monocytogenes in endosomes. Data from the present study indicate that proteose peptone-elicited macrophages from DBA2/J, CD-1, and C3H/HeN mice are listericidal. Activation of these cells in vitro for 20 h by IFN-gamma (20 or 500 U/ml) increased H2O2 or nitrite production, but did not increase the number of L. monocytogenes killed during a subsequent 6-h or 7-h culture. Incubation of macrophages with IFN-gamma plus lipopolysaccharide (LPS) caused greater activation and increased the number of Listeria killed during a 6-h or 7-h culture. However, this seems primarily attributable to enhanced phagocytosis. Proteose peptone-elicited macrophages were significantly more effective than resident macrophages in preventing the escape of L. monocytogenes from endosomes into the cytoplasm. This capability was not significantly enhanced by IFN-gamma in vitro, but was enhanced by IFN-gamma plus LPS. This correlates well with the effects of these activation stimuli on killing of L. monocytogenes by proteose peptone-elicited macrophages. These results indicate that enhanced retention of L. monocytogenes in endosomes is induced by proteose peptone elicitation and that further macrophage activation in vitro by IFN-gamma does not improve listericidal activity.
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PMID:Effect of macrophage activation on killing of Listeria monocytogenes. Roles of reactive oxygen or nitrogen intermediates, rate of phagocytosis, and retention of bacteria in endosomes. 160 35

A bacterial lipopolysaccharide (LPS)-resistant mutant was isolated from murine macrophagelike cell line J774.1. The mutant showed selective resistance to LPS and lipid A and was almost 10(5)- to 10(6)-fold more resistant than the parent; it grew even in the presence of 1 mg of Escherichia coli O55:B5 LPS per liter, whereas the parent did not grow with less than 10 ng of LPS per milliliter. We next examined the mutant for activation of various functions of macrophages on LPS treatment. This LPS-resistant mutant secreted interleukin-1 and tumor necrosis factor almost as effectively as the parent did. The mutant cells also changed transiently from a round to a spread form; however, they became round again afterwards. The mutant cells secreted less arachidonic acid in response to LPS. These results also suggest that this LPS-resistant mutant responds to LPS and shows activation of some macrophage functions. However, this mutant did not exhibit elevation of O2- generation or H2O2 generation after LPS treatment. Also, treatment of the mutant cells with murine recombinant gamma interferon was partly able to correct the defect in O(2-)-generating activity in response to LPS, suggesting that this defect is probably due to some of the LPS signal pathways. This implies that there is some correlation between O2- metabolism in LPS-activated macrophages and decreases in cell growth and viability.
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PMID:A lipopolysaccharide (LPS)-resistant mutant isolated from a macrophagelike cell line, J774.1, exhibits an altered activated-macrophage phenotype in response to LPS. 164 29

Thrombomodulin (TM) exists not only in endothelial cells but also in circulating plasma as soluble heterogeneous fragments. A release mechanism of soluble TM antigen from endothelial cells was investigated. Cultured human umbilical vein endothelial cells released about 0.6% of total cellular TM antigen into conditioned medium during 24 h. The release of TM antigen was not influenced by addition of various concentrations (0.01-5.0 microM) of monensin, which inhibits intracellular transport of secretory proteins, though the secretion of plasminogen activator inhibitor-1 from the cells was inhibited. The release of TM antigen was not increased when total cellular TM level increased 1.3- or 1.4-fold relative to control cells after stimulation with 0.1-1.0 U/ml thrombin or 3 mM dibutyryl cAMP, respectively. Exposure of endothelial cells for 6 h to mixture of 1 microM N-formyl-methionyl-leucyl-phenylalanine (FMLP) and 100 ng/ml lipopolysaccharide (LPS) decreased cellular TM level by 30% relative to control cells without increase in the TM release. The FMLP and LPS-stimulated leukocyte treatment of the cells increased the release of TM antigens into the medium in a time-dependent manner and the increased release of TM antigen paralleled the extent of cell damage as measured by 51Cr release. Hydrogen peroxide treatment of the cells increased the release of TM antigens into the medium in a time- and concentration-dependent manner. The increased release of TM antigen by hydrogen peroxide also paralleled the extent of cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. 165 69

The degranulation and myeloperoxidase-H2O2-halide activities of human polymorphonuclear leukocytes from healthy donors were tested after co-incubation with either Brucella melitensis 16M, Staphylococcus aureus or Staphylococcus aureus in presence of lipopolysaccharide, protein fraction, native hapten and soluble fractions released at 65 degrees C from smooth strain of Brucella melitensis 16M. The degranulation and myeloperoxidase activities of polymorphonuclear leukocytes were significantly higher when co-incubated with Staphylococcus aureus than with Brucella melitensis. The presence of lipopolysaccharide, protein fraction, and native hapten did not cause significant modification of either degranulation or myeloperoxidase activities of polymorphonuclear leukocytes against Staphylococcus aureus. Soluble fraction released at 65 degrees C produced a significant reduction in the myeloperoxidase activity but did not alter the degranulation of polymorphonuclear leukocytes triggered by Staphylococcus aureus.
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PMID:Inhibition of the degranulation and myeloperoxidase activity of human polymorphonuclear neutrophils by Brucella melitensis. 166 50

Increased secretion of H2O2, O2- and lysozyme by human monocytes in vitro on treatment with cisplatin, rIFN-Y (interferon-Y), LPS (lipopolysaccharide) and MDP (muramyl dipeptide) is reported. It is suggested that increased production of these secretory products represent the activated state of monocytes. These in vitro activated monocytes could either kill the tumor cells via increased contact mediated cytolysis or cytolysis mediated via the release of the secretory products like H2O2, O2- and lysozyme.
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PMID:Effect of cisplatin, rIFN-Y, LPS and MDP on release of H2O2, O2- and lysozyme from human monocytes in vitro. 166 47

We investigated the effects of platelet-activating factor (PAF) on guinea pig peritoneal macrophages. Specific and high-affinity binding sites for PAF were detected on guinea pig peritoneal macrophages. Scatchard analysis of PAF binding revealed high affinity binding sites (7.9 x 10(4)/cell) with a dissociation constant of 2.3 x 10(-10) M. When treated with 10(-9)-10(-5) M PAF, guinea pig peritoneal macrophages released hydrogen peroxide into the medium in a time-dependent manner. The release reaction upon stimulation with 10(-5) M PAF reached a plateau within 30 min and the extent of release was twice as high as that when stimulated by N-formyl-L-methionyl-leucyl-L-phenylalanine (fMLP; 2 microM)-treated cells. Neither lysoPAF nor the PAF enantiomer was effective. PAF-induced H2O2 release was inhibited specifically by PAF antagonists, suggesting that PAF activated macrophages through binding to specific sites. Lysosomal enzyme (N-acetyl-beta-D-glucosaminidase) was released from guinea pig peritoneal macrophages upon treatment with 10(-5) M PAF for 60 min. Guinea pig peritoneal macrophages were treated with PAF for 8 hr and the conditioned medium was examined for cytokines. The medium exhibited cytocidal activity against mouse fibroblast L929 cells [tumor necrosis factor (TNF) activity], and this activity was comparable to that detected after treatment of cells with the bacterial lipopolysaccharide (LPS). Furthermore, the same conditioned medium also showed colony-stimulating factor (CSF) activity. Generation of these cytokines was stereospecific. Our findings suggest that PAF is a unique macrophage activator that potentiates both respiratory burst/lysosomal enzyme release (early-phase response) and monokine production/glucose consumption (late-phase response).
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PMID:Biological response of guinea pig peritoneal macrophages to platelet-activating factor. 166 17

Phorbol 12-myristate 13-acetate-induced luminol chemiluminescence in rat Kupffer cells was doubled by the addition of L-arginine and significantly (up to 70%) inhibited by NG-nitro-L-arginine and NG-monomethyl-L-arginine, competitive inhibitors of L-arginine-dependent nitric oxide (NO) formation. The release of superoxide anion (O2-) by NADPH oxidase was neither affected by L-arginine nor by the inhibitors. Only very slight luminol chemiluminescence was detectable in lipopolysaccharide-pretreated Kupffer cells, a condition in which significant amounts of NO were formed but no O2-. In a cell-free system, significant luminol chemiluminescence only occurred when both authentic NO and the O2-/H2O2- generating system xanthine/xanthine oxidase were present. The results indicate that luminol chemiluminescence in phorbol-ester-activated Kupffer cells largely depends on L-arginine metabolism by NO synthase, requiring the concurrent formation of NO and O2-/H2O2.
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PMID:Contribution of nitric oxide synthase to luminol-dependent chemiluminescence generated by phorbol-ester-activated Kupffer cells. 171 62

Pregnant randombred ICR mice were administered 2.5 or 5.0 mg/kg body weight of CdCl2 on day 16 of pregnancy and immune responses of their offspring were tested postnatally. At the age of 4 weeks, proliferative responses of spleen cells to concanavalin A, phytohemagglutinin and lipopolysaccharide and the background proliferation were enhanced in both experimental groups. The activation index was increased only after activation with concanavalin A and lipopolysaccharide in the group treated by the dose 5 mg/kg. The delayed type hypersensitivity to sheep red blood cells after immunization at 4 weeks was decreased. The serum IgM antibody response to sheep red blood cells was increased in the offspring of females treated with the lower dose of cadmium both at week 4 and 8. Activity of peritoneal macrophages (NBT, H2O2) was enhanced at 4 weeks and lowered subsequently. It is concluded that in mice the maternal exposure to a single dose of cadmium results in postnatally manifested deviations of immune functions of their offsprings.
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PMID:Developmental toxicity of cadmium in mice. II. Immunotoxic effects. 181 May 12


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