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 aim of the present study was to analyse whether an increase in the intracellular free Ca2+ concentration ([Ca2+]i) plays a role as a signal mediating synthesis of nitric oxide (NO) in bone-marrow-derived macrophages, either by stimulating induction of NO synthase or by regulating the activity of the enzyme. Therefore we compared the effects of various synthetic analogues of bacterial lipopeptide and of lipopolysaccharide (LPS) on NO production (assessed as nitrite formation during an incubation for 24 h) and on [Ca2+]i [measured with the fluorescent probe indo-1 (1-[2-amino-5-(6-carboxyindol-2-yl)phenoxy]-2- 2-(2'-amino-5'-methylphenoxy)ethane-NNN'N'-tetra-acetic acid)]. Strongly dissociating effects were evoked on nitrite formation and on [Ca2+]i by the stimuli. LPS was preferentially effective on nitrite formation, whereas the Ca2+ ionophore ionomycin and AlF3 induced increases only in [Ca2+]i. The lipopeptides N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)- propyl]-(R)-cysteinylalanylglycine, N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)- (2RS)-propyl]-(R)-cysteinylseryl-lysyl-lysyl-lysine and (S)-(1,2- dicarboxyhexadecyl)ethyl-N-palmitoylcysteinylseryl-lysyl-lys yl-lysine stimulated both parameters, but the maximal effects on nitrite formation and the shape of the dose-response curves did not parallel the effects on [Ca2+]i. Reduction of extracellular Ca2+ with EGTA significantly inhibited increases in [Ca2+]i, but did not change nitrite formation. Furthermore, NO synthesis in the cytosolic fraction of stimulated macrophages was not affected by Ca2+ over the concentration range 10 nM-2 microM. We conclude that increases in [Ca2+]i are not required for NO production in bone-marrow-derived macrophages. Thus the cellular regulation of NO production strikingly differs from that in the vascular endothelium, brain and adrenal gland.
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PMID:Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+. 169 56

The transport of cationic amino acids has been investigated in mouse peritoneal macrophages cultured in vitro. The transport activity for lysine was rather low in cells cultured for 1 h and increased slightly in cells cultured for 12 h. This increase varied with the serum lot used in the culture medium and was suppressed by polymyxin B, suggesting that the transport activity is induced by endotoxins in the serum. When the macrophages were cultured in the medium containing 1 ng/ml lipopolysaccharide, the transport activity for lysine increased by more than 10-fold. The transport activity for lysine induced by lipopolysaccharide has been characterized. Lysine was transported mainly by a Na(+)-independent, saturable system. The uptake of lysine was potently inhibited by extracellular cationic amino acids, but not by neutral amino acids tested. In addition, transport of lysine showed trans-stimulation. From these results, we have concluded that the transport activity for cationic amino acids is potently induced by lipopolysaccharide and that the characteristics of the induced activity is consistent with those of system y+.
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PMID:Induction of cationic amino acid transport activity in mouse peritoneal macrophages by lipopolysaccharide. 193 48

The nucleotide sequences of two mink serum amyloid A (SAA) cDNA clones have been analyzed, one (SAA1) 776 base pairs long and the other (SAA2) 552 base pairs long. Significant differences were discovered when derived amino acid sequences were compared with data for apoSAA isolated from high density lipoprotein. Previous studies of mink protein SAA and amyloid protein A (AA) suggest that only one SAA isotype is amyloidogenic. The cDNA clone for SAA2 defines the "amyloid prone" isotype while SAA1 is found only in serum. Mink SAA1 has alanine in position 10, isoleucine in positions 24, 67, and 71, lysine in position 27, and proline in position 105. Residue 10 in mink SAA2 is valine while arginine and asparagine are at positions 24 and 27, respectively, all characteristics of protein AA isolated from mink amyloid fibrils. Mink SAA2 also has valine in position 67, phenylalanine in position 71, and amino acid 105 is serine. It remains unknown why these six amino acid substitutions render SAA2 more amyloidogenic than SAA1. Eighteen hours after lipopolysaccharide stimulation, mink SAA mRNA is abundant in liver with relatively minor accumulations in brain and lung. Genes encoding both SAA isotypes are expressed in all three organs while no SAA mRNA was detectable in amyloid prone organs, including spleen and intestine, indicating that deposition of AA from locally synthesized SAA is unlikely. A third mRNA species (2.2 kilobases) was identified and hybridizes with cDNA probes for mink SAA1 and SAA2. In addition to a major primary translation product (molecular mass 14,400 Da) an additional product with molecular mass 28,000 Da was immunoprecipitable.
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PMID:Mink serum amyloid A protein. Expression and primary structure based on cDNA sequences. 235 48

Macrophages consume cystine and generate approximately equivalent amounts of acid-soluble thiol. Stimulation of macrophages with bacterial lipopolysaccharide (LPS) or tumor necrosis factor (TNF) strongly augments the amount of thiol released into the culture supernatant. Cysteine constitutes most of the acid-soluble thiol. The intracellular glutathione level and the DNA synthesis activity in mitogenically stimulated lymphocytes are strongly increased by either exogenously added cysteine, or (syngeneic) macrophages. This cysteine dependency is observed even in the presence of relatively high extracellular cystine concentration as they occur in the blood plasma. The extracellular cysteine concentration also has a strong influence on the intracellular glutathione concentration, viability, and DNA synthesis of cycling T cell clones. Moreover, the cysteine concentration in the culture medium on Day 3 and Day 4 of a 5-day allogeneic mixed lymphocyte culture (i.e., in the late phase of incubation) has a strong influence on the generation of cytotoxic T cell activity, indicating that regulatory effects of cysteine are not restricted to the early phase of the blastogenic response. The inhibitory effect of cysteine starvation on the DNA synthesis of the T cell clones and on the activation of cytotoxic T lymphocytes can be explained essentially by the depletion of intracellular glutathione, since similar effects are observed after treatment with buthionine sulfoximine (BSO), a specific inhibitor of the glutathione biosynthesis. BSO has practically no influence, however, on the N alpha-benzyloxycarbonyl Ne-t-butyloxycarbonyl-L-lysine-thiobenzyl-ester (BLT)-esterase activity and hemolytic activity of the cell lysates from cytotoxic T cells against sheep red blood cells (perforin activity). Taken together, our experiments indicate that cysteine has a regulatory role in the immune system analogous to the hormone-like lymphokines and cytokines. It is released by macrophages at a variable and regulated rate and regulates immunologically relevant functions of lymphocytes in the vicinity.
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PMID:Macrophages regulate intracellular glutathione levels of lymphocytes. Evidence for an immunoregulatory role of cysteine. 236 41

Experiments were conducted to determine the influence of immunologic stress on methionine and lysine requirements of growing chicks. Immunologic stress was elicited by injection of either Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus every other day for 6 d. In the first experiment, diets were formulated to provide methionine levels of 0.30, 0.50 and 0.70%. In the second experiment, diets contained 0.75, 0.90 or 1.2% lysine. In chicks fed amino acid-sufficient diets, those chicks injected with immunogens had slower growth, lower feed intake and poorer efficiency of feed utilization than those injected with saline. The decreases due to immunogens were diminished in chicks fed amino acid-deficient diets. The methionine requirements of saline- and immunogen-injected chicks were above 0.5% and between 0.3 and 0.5%, respectively; the lysine requirements were greater than 0.95% and between 0.7 and 0.95%, respectively. Thus immunogen injection decreased methionine and lysine requirements, probably because of a decreased need of amino acids for growth and tissue accretion. Immunogen-induced depression in serum zinc and increase in serum copper levels were ameliorated by lysine or methionine deficiencies. Compared with saline-injected chicks, immunogen-injected chicks had significantly higher serum interleukin-1 (IL-1) activity by 53% when fed the methionine-sufficient diet, but they did not have significantly greater IL-1 levels when fed the methionine-deficient diet. These observations indicate that the diminished expression of immunologic stress in amino acid-deficient chicks is due to an impaired immune response.
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PMID:Decreased amino acid requirements of growing chicks due to immunologic stress. 245 41

Collagenolytic enzyme release from bone cells was studied using cultured calvarial cells which are capable of degrading calcified and noncalcified collagen (cells from normal mice) or only noncalcified collagen (cells from osteopetrotic (mi/mi) mice). Treatment of cells from either normal or mi/mi mice with parathyroid hormone (PTH) or lipopolysaccharide (LPS) resulted in the appearance of latent collagenolytic enzyme activity in the medium. Chromatography of media from cells from normal mice treated with PTH on lysine-Sepharose resulted in the separation of latent collagenase and latent gelatinase. Further characterization of the enzymes showed that they were similar to those previously isolated from media of calvaria cultured with heparin. Collagenase activity of media of cells from normal or mi/mi mice treated with PTH or LPS yielded identical elution patterns upon chromatography on lysine-Sepharose. These results show that the mi allele has no effect on regulation of latent collagenolytic enzyme release. The results show that the mi allele has no effect on regulation of latent collagenolytic enzyme release. The data also suggest that previously described differences between PTH- and LPS-stimulated collagen degradation in cultured calvaria are due to factors other than differences in the ability of these agents to stimulate the release of collagenolytic enzymes.
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PMID:Stimulation of collagenolytic enzyme release from cultured bone cells of normal and osteopetrotic (mi/mi) mice by parathyroid hormone and lipopolysaccharide. 254 66

The effect of muramyldipeptide (MDP), glucosaminylmuramyldipeptide (GMDP) and their six synthetic derivatives on production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-2 (IL-2) by murine spleen cells in vitro was studied. MDP induced insignificant TNF production and did not stimulate production of IL-1 by the murine splenocytes within a 24-hour cultivation period whereas in combination with lipopolysaccharide (LPS) it induced significant production of both the cytokins. GMDP induced marked production of TNF (54 per cent cytotoxic index) and IL-1 (stimulation index 8). Addition of LPS in an amount of 10 ng/ml increased production of TNF by the murine splenocytes under the effect of GMDP but had no effect on production of IL-1. Neither MDP nor GMDP even in combination with LPS induced production of IL-2 by splenocytes of mice DVA/2 and C57B1/6 at activation for 24 hours. All the synthetic derivatives of MDP and GMDP except the MDP polymer activated TNF production by the murine spleen cells. GMDP lysine had the highest effect: 67 per cent cytotoxic index. In combination with LPS its cytotoxic index amounted to 87 per cent. The TNF activity was always higher when LPS in an amount of 10 ng/ml was added to the glycopeptides.
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PMID:[Immunostimulating effects of muramyl dipeptide, glucosaminyl muramyl dipeptide and their synthetic derivatives in vitro]. 258 97

Conjugation of simple ketoses (such as 3-deoxy-D-manno-2-octulosonic acid and N-acetylneuraminic acid) and of various O-specific polysaccharides (from Aeromonas hydrophila and Aeromonas salmonicida) to the bifunctional spacer 1,6-hexanediamine, was achieved by reductive amination. The saccharide--1-(6-amino)-hexane alkyamines obtained were converted into the corresponding isothiocyanate derivatives and coupled to the free epsilon-amino group of lysine residues of the protein carrier bovine serum albumin. In similar manner, the aldehyde group introduced by selective periodate oxidation into the partially O-deacylated lipopolysaccharide of Vibrio anguillarum was conjugated to 1,6-hexanediamine, converted into the corresponding isothiocyanate and covalently attached to bovine serum albumin.
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PMID:Synthesis of glycoconjugates derived from various lipopolysaccharides of the Vibrionaceae family. 292 Jul 31

Cells of two smooth Salmonella typhimurium strains (SL696 and SH4247) were treated with ethylenediaminetetraacetic acid (EDTA) and the polycations poly(L-lysine) and protamine to monitor both quantitatively and qualitatively the release of [14C] galactose-labelled lipopolysaccharide into the medium to find out whether these effector substances caused selective release of certain fractions from the initially heterogenous lipopolysaccharide population. Each one of the substances released considerable amounts of lipopolysaccharide into the medium. Analysis by sodium dodecyl sulphate/polyacrylamide gel electrophoresis followed by autoradiography showed that the total lipopolysaccharide (from isolated membranes) and the released materials produced coincident banding patterns, each with a high degree of O side-chain length heterogeneity. Densitometric scans of the autoradiograms were analyzed for possible differences in the distribution and relative abundance of lipopolysaccharide molecules with different O chain lengths. It was found that in SL696 the released materials were identical to the total lipopolysaccharide; in SH4247 subtle deviations from the total lipopolysaccharide were seen. We conclude from these results that lipopolysaccharide molecules with short and long O side chains are linked to and stabilized in the outer membrane by similar mechanisms equally susceptible to the effects of EDTA and polycations.
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PMID:Chain length heterogeneity of lipopolysaccharide released from Salmonella typhimurium by ethylenediaminetetraacetic acid or polycations. 308 44

When human serum was incubated at 45 degrees C for 30 min, C3 and B were converted to C3b and Bb. Molecular weights of purified C3 and B were shown not to change after incubation at 50 degrees C. Spectropolarimetry indicated that the secondary structures of C3 and B changed after incubation at higher temperature. The titration of SH groups in the C3 molecule showed the liberation of an SH group. These results show that the alternative complement pathway is activated at raised temperatures without known activators such as zymosan or lipopolysaccharide (LPS). This may be due to the accelerated interaction of conformationally changed components of the alternative pathway such as C3 and B. Using this system, effects of various substances on the interaction of C3 and B in serum and the purified system were investigated. The addition of arginine and lysine resulted in the inhibition of the conversion of C3 and B in the serum at elevated temperature. Other amino acids such as anionic amino-acids and NaCl did not influence the conversion. In the purified system, only arginine and lysine prevented the conversion of C3 and B, when C3, B and D were incubated in the presence of Mg++ and amino-acids. Since lysine and arginine did not inhibit the enzymatic activity of D, these data suggest that arginine and lysine prevent the interaction of C3 and B in the serum at elevated temperatures.
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PMID:Inhibition by lysine and arginine of the conversion of C3 and B in the serum and a purified system. 308 51


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