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 body's protective responses to infection, wounding, trauma, and malignancy include the acute-phase reaction, which is modulated by various cytokines and their cellular receptors. During the acute-phase reaction, levels of specific proteins synthesized by the liver increase in the plasma. Little information is available about the extrahepatic synthesis of plasma proteins during the acute-phase reaction. The study described here analyzes the tissue-specific expression of genes encoding the plasma proteins albumin (ALB), alpha 1-antitrypsin (AAT), transferrin (TF), haptoglobin (HP), ceruloplasmin (CP), serum amyloid A (SAA), alpha 1-acid glycoprotein (AGP) and alpha 2-HS-glycoprotein (AHSG) during the acute-phase reaction in C57B1 mice. The acute-phase reaction was induced by intraperitoneal injections of bacterial lipopolysaccharide (LPS). During the acute-phase reaction, genes encoding CP, SAA, AGP, and HP demonstrate unique extrahepatic tissue specific patterns of expression in kidney, spleen, thymus, heart, brain, lung, testis, and epididymis. Different temporal patterns of HP gene expression also were observed in lung and thymus after induction by LPS. The function of extrahepatic synthesis of plasma proteins is not yet understood; however, a local provision of specific plasma proteins in mammalian tissues may offer the host a source of functionally important proteins during periods of stress.
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PMID:Extrahepatic expression of plasma protein genes during inflammation. 175 24

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

We have developed a method to control the effective time period of (1----3)-beta-D-glucan in vivo by using (1----3)-beta-D-glucanase and found that grifolan LE (GRN), a (1----3)-beta-D-glucan, administered intraperitoneally to the host required more than 2 d to exert antitumor activity. During these two days many immunological changes were induced, such as increasing the number of peritoneal exudated cells (PEC), augmentation of production of interleukin 1 (IL-1), acid phosphatase and phagocytic capacity of adherent cells in PEC. In addition, there was increased carbon clearance activity in vivo, augmentation of responsiveness of splenocytes to mitogens such as concanavalin A and lipopolysaccharide (LPS) and production of ceruloplasmin. When (1----3)-beta-D-glucanase was injected 1 d after GRN administration, IL-1 productivity and responsiveness to LPS were significantly reduced, but lysosomal enzyme activity and phagocytosis of macrophage and production of ceruloplasmin were similar to those not treated with glucanase. These facts indicate that the induction of the activities of the former group requires longer contact of host cells with the glucan, and the latter group requires a shorter period to achieve fully active stages.
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PMID:Modification of immunostimulating activities of grifolan by the treatment with (1----3)-beta-D-glucanase. 263 64

From birth mice received diets containing copper at 0.5, 1, 2 or 6 mg/kg diet. At 8 wk of age they were killed and copper status and immune responsiveness were determined. Only the groups that received copper at 0.5 or 1 mg/kg showed signs of copper deficiency, such as reduced serum ceruloplasmin, hemoglobin, hematocrit and red blood cell counts and characteristic changes in organ pathology. Body and lymphoid organ weights were altered in the groups that received copper at 0.5 or 1 mg/kg. Males were more severely affected than females. A dose-related reduction in splenic T-cell subpopulations was noted in the 0.5 and 1 mg/kg groups. Responses to lipopolysaccharide challenge were reduced, and an increase in spontaneous cycling cells was noted in the groups receiving copper at 0.5 or 1 mg/kg. Only the group receiving copper at 0.5 mg/kg had increased stem cell activity; this increase was probably due to increased erythropoiesis to meet increased demands for red blood cells in this group. These data indicate that only groups receiving copper at 0.5 or 1 mg/kg in the diet were depleted and marginally depleted in copper, respectively, and that immune hyporesponsiveness differs between the depleted and marginally depleted groups.
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PMID:Severe or marginal copper deficiency results in a graded reduction in immune status in mice. 326 38

The antipyretic properties of copper (II) salicylate and its effect on plasma copper, iron, zinc and ceruloplasmin concentrations was investigated in adult rabbits at an ambient temperature of 21.5 +/- 0.5 degrees C. The experiments indicated that copper salicylate (200 mg/kg/h i.v.) was a more potent antipyretic than sodium salicylate given in the same manner and doses. This pharmacological activity was found on a model of experimental fever induced by i.v. injection of lipopolysaccharide Escherichia coli at a dose of 1 microgram/kg. Furthermore, unlike sodium salicylate, this copper complex caused a decrease in core temperature in normothermic rabbits. At the same time copper salicylate activated heat dissipation much more efficiently than the parent drug, as manifested by decreases in vasomotor tone and reversal of postpyrogen inhibition of RF. As was expected, treatment with copper salicylate increased plasma copper and ceruloplasmin levels in both normothermic and febrile rabbits. These increases did not lead to any disturbances in iron and zinc concentrations. Neither salicylate affected postpyrogen falls in plasma iron concentrations. They both, however, delayed the appearance of zinc decreases in febrile rabbits. The results of this study suggest that copper modifies the thermoregulatory effects of salicylate. Moreover, the increased amounts of this metal do not seem to disturb seriously the ionic status of the blood.
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PMID:Copper salicylate complex: thermoregulatory and biochemical effects. 383 71

Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA. 781 Jul 70

We investigated the effect of plasma ceruloplasmin (Cp) on the different types of lymphocyte rosetting, and phagocytosis of polystyrene particles and culture Candida albicans by peripheral blood neutrophils and monocytes. Lymphocytes, neutrophils, and monocytes were isolated from the blood of patients with elevated immuno-status (n = 9), healthy donors (n = 21), and patients with reduced immuno-status (n = 21). The ability of Cp to decrease the number of lymphocytes forming E- and EAC-rosettes and rosettes with auto-erythrocytes was shown for both patients and healthy donors. The maximal decrease of the number of E-rosettes (by 35%) and EAC-rosettes (by 57%) was shown for lymphocytes of the patients with elevated immuno-status. Cp had an effect on rosetting only when lymphocytes were preincubated with it, suggesting that Cp binding to lymphocytes was responsible for these effects. The decrease in all types of rosetting caused by Cp was dose-related, with a maximum effect at physiological concentration of Cp (300 micrograms/ml). We demonstrated an enhancing effect of Cp on phagocytosis of Candida albicans and polystyrene particles by neutrophils (with a maximum enhancement by 180% for neutrophils of the patients with decreased immuno-status) and monocytes (with a maximum of 89% for monocytes of healthy donors). Cp enhances phagocytosis of neutrophils and monocytes by binding these cells, not by opsonizing ingested particles as a conventional opsonin (ie. lipopolysaccharide from E.coli). The stimulating effect of Cp on phagocytosis was three times higher than that of LPS from E.coli.
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PMID:Modulatory effects of ceruloplasmin on lymphocytes, neutrophils and monocytes of patients with altered immune status. 819 58

Two experiments were conducted to examine the effect of dietary Cu level on Cu metabolism during the acute phase response in broiler chicks with adequate (Experiment 1) or deficient (Experiment 2) Cu. Diets based on cornstarch and isolated soybean protein were used to formulate a basal diet, and basal diet plus either 5, 10, or 15 mg/kg additional Cu as either CuO or CuSO4. Each diet was fed to six pens of five chicks per pen (Experiment 1) or eight pens of five chicks (Experiment 2). Half of the chicks on each diet were injected with Salmonella typhymurium lipopolysaccharide (LPS) on alternate days. In Experiment 1, LPS significantly decreased daily gain, feed intake, and feed efficiency (P < 0.01) and increased the concentration of Cu in blood plasma (P < 0.01). In the uninjected birds, adding 5, 10, or 15 mg/kg Cu as CuO or 15 mg/kg Cu as CuSO4 increased the rate of gain over that of chicks fed the basal diet. In the birds challenged with LPS, 10 mg/kg Cu as CuO increased the rate of gain and efficiency compared to those of chicks fed the basal diet. Addition of CuSO4 to the diet of chicks challenged with LPS did not affect gain, intake, or feed efficiency compared to those of chicks fed the basal diet. Ceruloplasmin levels were higher in chicks challenged with LPS than in control chicks (P = 0.03), and this difference tended to be greater in chickens fed CuO than in chickens fed CuSO4 (P = 0.07). In chicks challenged with LPS, feeding CuO at all levels and feeding CuSO4 to give 10 or 15 mg/kg Cu increased ceruloplasmin levels above that of chicks fed the basal diet. Hepatic Mn superoxide dismutase (SOD) and Cu/Zn SOD were not influenced by dietary Cu level or source or LPS. Results of Experiment 2 were similar to those of Experiment 1 except that supplemental CuSO4 and CuO gave similar increases in gain and CuSO4 was more effective at increasing ceruloplasmin levels. Chicks given supplemental Cu had higher ceruloplasmin levels following challenge with LPS than Cu-deficient chicks fed the basal diet. Apparently, Cu requirements are higher for chicks experiencing an acute phase response than for healthy chicks.
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PMID:Dietary copper level affects copper metabolism during lipopolysaccharide-induced immunological stress in chicks. 880 5

The liver lobule is formed by parenchymal cells, i.e., hepatocytes and nonparenchymal cells. In contrast to hepatocytes that occupy almost 80% of the total liver volume and perform the majority of numerous liver functions, nonparenchymal liver cells, which contribute only 6.5% to the liver volume, but 40% to the total number of liver cells, are localized in the sinusoidal compartment of the tissue. The walls of hepatic sinusoid are lined by three different cell types: sinusoidal endothelial cells (SEC), Kupffer cells (KC), and hepatic stellate cells (HSC, formerly known as fat-storing cells, Ito cells, lipocytes, perisinusoidal cells, or vitamin A-rich cells). Additionally, intrahepatic lymphocytes (IHL), including pit cells, i.e., liver-specific natural killer cells, are often present in the sinusoidal lumen. It has been increasingly recognized that both under normal and pathological conditions, many hepatocyte functions are regulated by substances released from neighboring nonparenchymal cells. Liver sinusoidal endothelial cells constitute the lining or wall of the hepatic sinusoid. They perform important filtration function due to the presence of small fenestrations that allow free diffusion of many substances, but not of particles of the size of chylomicrons, between the blood and the hepatocyte surface. SEC show huge endocytic capacity for many ligands including glycoproteins, components of the extracellular matrix (ECM; such as hyaluronate, collagen fragments, fibronectin, or chondroitin sulphate proteoglycan), immune complexes, transferrin and ceruloplasmin. SEC may function as antigen-presenting cells (APC) in the context of both MHC-I and MHC-II restriction with the resulting development of antigen-specific T-cell tolerance. They are also active in the secretion of cytokines, eicosanoids (i.e., prostanoids and leukotrienes), endothelin-1, nitric oxide, and some ECM components. Kupffer cells are intrasinusoidally located tissue macrophages with a pronounced endocytic and phagocytic capacity. They are in constant contact with gut-derived particulate materials and soluble bacterial products so that a subthreshold level of their activation in the normal liver may be anticipated. Hepatic macrophages secrete potent mediators of the inflammatory response (reactive oxygen species, eicosanoids, nitric oxide, carbon monoxide, TNF-alpha, and other cytokines), and thus control the early phase of liver inflammation, playing an important part in innate immune defense. High exposure of Kupffer cells to bacterial products, especially endotoxin (lipopolysaccharide, LPS), can lead to the intensive production of inflammatory mediators, and ultimately to liver injury. Besides typical macrophage activities, Kupffer cells play an important role in the clearance of senescent and damaged erythrocytes. Liver macrophages modulate immune responses via antigen presentation, suppression of T-cell activation by antigen-presenting sinusoidal endothelial cells via paracrine actions of IL-10, prostanoids, and TNF-alpha, and participation in the development of oral tolerance to bacterial superantigens. Moreover, during liver injury and inflammation, Kupffer cells secrete enzymes and cytokines that may damage hepatocytes, and are active in the remodeling of extracellular matrix. Hepatic stellate cells are present in the perisinusoidal space. They are characterized by abundance of intracytoplasmic fat droplets and the presence of well-branched cytoplasmic processes, which embrace endothelial cells and provide focally a double lining for sinusoid. In the normal liver HSC store vitamin A, control turnover of extracellular matrix, and regulate the contractility of sinusoids. Acute damage to hepatocytes activates transformation of quiescent stellate cells into myofibroblast-like cells that play a key role in the development of inflammatory fibrotic response. Pit cells represent a liver-associated population of large granular lymphocytes, i.e., natural killer (NK) cells. They spontaneously kill a variety of tumor cells in an MHC-unrestricted way, and this antitumor activity may be enhanced by the secretion of interferon-gamma. Besides pit cells, the adult liver contains other subpopulations of lymphocytes such as gamma delta T cells, and both "conventional" and "unconventional" alpha beta T cells, the latter containing liver-specific NK T cells. The development of methods for the isolation and culture of main liver cell types allowed to demonstrate that both nonparenchymal and parenchymal cells secrete tens of mediators that exert multiple paracrine and autocrine actions. Co-culture experiments and analyses of the effects of conditioned media on cultures of another liver cell type have enabled the identification of many substances released from non-parenchymal liver cells that evidently regulate some important functions of neighboring hepatocytes and non-hepatocytes. To the key mediators involved in the intercellular communication in the liver belong prostanoids, nitric oxide, endothelin-1, TNF-alpha, interleukins, and chemokines, many growth factors (TGF-beta, PDGF, IGF-I, HGF), and reactive oxygen species (ROS). Paradoxically, the cooperation of liver cells is better understood under some pathological conditions (i.e., in experimental models of liver injury) than in normal liver due to the possibility of comparing cellular phenotype under in vivo and in vitro conditions with the functions of the injured organ. The regulation of vitamin A metabolism provides an example of the physiological role for cellular cross-talk in the normal liver. The majority (up to 80%) of the total body vitamin A is stored in the liver as long-chain fatty acid esters of retinal, serving as the main source of retinoids that are utilized by all tissues throughout the body. Hepatocytes are directly involved in the uptake from blood of chylomicron remnants, and the synthesis of retinol-binding protein that transfers retinol to other tissues. However, more than 80% of the liver retinoids are stored in lipid droplets of hepatic stellate cells. HSC are capable of both uptake and release of retinol depending on the body's retinol status. The activity of some major enzymes of vitamin A metabolism have been found to be many times higher per protein basis in stellate cells than in hepatocytes. Despite progress in the understanding of the roles played by these two cell types in hepatic retinoid metabolism, the way in which retinoids move between the parenchymal cells, stellate cells, and blood plasma has not been fully elucidated. Sinusoidal blood flow is, to a great extent, regulated by hepatic stellate cells that can contract due to the presence of smooth muscle alpha-actin. The main vasoactive substances that affect constriction or relaxation of HSC derive both from distant sources and from neighboring hepatocytes (carbon monoxide, leukotrienes), endothelial cells (endothelin, nitric oxide, prostaglandins), Kupffer cells (prostaglandins, NO), and stellate cells themselves (endothelin, NO). The cellular cross-talk reflected by the fine-tuned modulation of sinusoidal contraction becomes disturbed under pathological conditions, such as endotoxemia or liver fibrosis, through the excess synthesis of vasoregulatory compounds and the involvement of additional mediators acting in a paracrine way. The liver is an important source of some growth factors and growth factor-binding proteins. Although hepatocytes synthesize the bulk of insulin-like growth factor I (IGF-I), also other types of nonparenchymal liver cells may produce this peptide. Cell-specific expression of distinct IGF-binding proteins observed in the rat and human liver provides the potential for specific regulation of hepatic IGF-I synthesis not only by growth hormone, insulin, and IGF-I, but also by cytokines released from activated Kupffer (IL-1, TNF-alpha, TGF-beta) or stellate cells (TGF-alpha, TGF-beta). Hepatic stellate cells may affect turnover of hepatocytes through the synthesis of potent positive as well as negative signals such as, respectively, hepatocyte-growth-factor or TGF-beta. Although hepatocytes seem not to produce TGF-beta, a pleiotropic cytokine synthesized and secreted in the latent form by Kupffer and stellate cells, they may contribute to its actions in the liver by the intracellular activation of latent TGF-beta, and secretion of the biologically active isoform. Many mediators that reach the liver during inflammatory processes, such as endotoxins, immune-complexes, anaphylatoxins, and PAF, increase glucose output in the perfused liver, but fail to do so in isolated hepatocytes, acting indirectly via prostaglandins released from Kupffer cells. In the liver, prostaglandins synthesized from arachidonic acid mainly in Kupffer cells in a response to various inflammatory stimuli, modulate hepatic glucose metabolism by increasing glycogenolysis in adjacent hepatocytes. The release of glucose from glycogen supports the increased demand for energetic fuel by the inflammatory cells such as leukocytes, and additionally enables enhanced glucose turnover in sinusoidal endothelial cells and Kupffer cells which is necessary for effective defense of these cells against invading microorganisms and oxidative stress in the liver. Leukotrienes, another oxidation product of arachidonic acid, have vasoconstrictive, cholestatic, and metabolic effects in the liver. A transcellular synthesis of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) functions in the liver: LTA4, an important intermediate, is synthesized in Kupffer cells, taken up by hepatocytes, converted into the potent LTC4, and then released into extracellular space, acting in a paracrine way on Kupffer and sinusoidal endothelial cells. Thus, hepatocytes are target cells for the action of eicosanoids and the site of their transformation and degradation, but can not directly oxidate arachidonic acid to eicosanoids. (ABSTRACT TRUNCATED)
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PMID:Cooperation of liver cells in health and disease. 1172 49

We have previously shown that iron-containing human lactoferrin (LF) purified from breast milk is able to form both in vitro and in vivo a complex with ceruloplasmin (CP), the copper-containing protein of human plasma. Here we present evidence that the CP-LF complex is dissociated by high concentrations of NaCl, CaCl2, or EDTA, or by decreasing the pH to 4.7. In addition, DNA, bacterial lipopolysaccharide, and heparin can displace CP from its complex with LF. Antibodies to either of the two proteins also cause dissociation of the complex.
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PMID:Studies of the ceruloplasmin-lactoferrin complex. 1190 41


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