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)

We studied 75 BALB/c mice to examine the role of impaired immunoglobulin M (IgM) synthesis in the increased risk of bacterial infection after burn injury by investigating the kinetics of IgM synthesis to peptidoglycan polysaccharide (PGPS), a ubiquitous bacterial antigen. Splenocytes were isolated 1, 5, and 8 days postburn (PBD) and cultured with lipopolysaccharide for 5 days. Culture supernatant was collected and anti-PGPS IgM and total IgM levels were measured by ELISA. Total IgM-secreting cells were measured by ELISPOT assay. Total IgM and anti-PGPS IgM per IgM-secreting cell were calculated. On PBD 1, anti-PGPS IgM synthesis but not total IgM synthesis is increased in burned animals. By PBD 5, total IgM and anti-PGPS IgM synthesis in the burn group start to fall and by PBD 8, both are significantly decreased. The early increase in anti-PGPS IgM synthesis represents a positive response to bacterial challenge. However, the late nonspecific decrease in total IgM and anti-PGPS IgM synthesis suggests a potential mechanism for increased susceptibility to bacterial infection 5 to 10 days after burn injury.
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PMID:Burn injury induces a biphasic immunoglobulin M response to bacterial antigen. 767 97

It has been generally agreed that the elderly had a greater susceptibility, morbidity, and mortality in regard to a variety of bacterial infections. To clarify the host defence mechanism in the elderly, we studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil functions, the production of G-CSF by peripheral blood monocytes in response to lipopolysaccharide (LPS) and the serum levels of G-CSF in patients with bacterial pneumonia. There was no significant difference in the phagocytic activity of neutrophils between the elderly and control young adults. rhG-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both group. Killing activity of neutrophils assessed by the new nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment with rhG-CSF resulted in an increase of killing activity in the elderly, raising their response to a level compatible to that of young adults pretreated with rhG-CSF. The amount of G-CSF in the culture supernatants from LPS-stimulated peripheral blood monocytes of the elderly was significantly lower than that of young adults (p < 0.05). The serum levels of G-CSF in the acute phase of bacterial pneumonia in the elderly were significantly lower than those of young adults (p < 0.01). These results indicated that impaired monocyte function may contribute, at least in part, to susceptibility to bacterial infection in the elderly.
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PMID:[The role of G-CSF in host defense mechanisms of the elderly]. 768 69

We postulated that defective generation of granulocyte colony-stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.
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PMID:Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates. 840 Feb 78

Monocyte derived cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were determined in cell free plasma after stimulation of heparinized whole blood from chronic lymphocytic leukemia (CLL) patients with lipopolysaccharide (LPS) at 1 microgram/ml for 6 hr. Compared to control donors (390 U/ml), CLL patients in average had eight-fold lower levels of TNF bioactivity (50 U/ml). The depressed levels were observed over a wide range of LPS concentrations (0.01 to 10 micrograms/ml). Furthermore, after stimulation with S. aureus bacteria, CLL samples gave three-fold lower levels, as well. TNF levels were not decreased because of defective bioactivity of TNF, since strongly reduced levels of TNF protein were also detected in an immunoassay. Finally, interleukin-6 levels after LPS stimulation were decreased threefold. Flow cytometry analysis with CD14 antibodies demonstrated comparable numbers of monocytes for control donors and CLL patients (698 +/- 802 and 427 +/- 267, respectively). This suggests that deficient cytokine production was not due to a reduction in monocyte number, but rather to a functional impairment. The deficiency in cytokine production observed after ex vivo stimulation of whole blood from CLL patients suggests that in vivo during bacterial infection, CLL patients will exhibit an inappropriate response as well.
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PMID:Decreased production of TNF and IL-6 in whole blood of CLL patients. 774 Nov 43

A naturally occurring hemagglutinin was detected in the serum of the hermit crab Diogenes affinis, and its erythrocyte (RBC) binding activities, physicochemical properties, and carbohydrate binding specificity were characterized. Both the hemagglutination profile and the pattern of cross-reactivity of the serum with different RBC types in cross-adsorption tests suggested a strong affinity of the serum agglutinin for rat RBC. Further analysis revealed that the agglutinin was specifically dependent on Ca2+ for its hemagglutinating activity and reversibly sensitive to EDTA. The activity was found to be stable between pH 6.0 and 7.5, heat-labile, and completely precipitable by ammonium sulphate or TCA, suggesting the proteinaceous nature of the serum agglutinin. In hemagglutination-inhibition assays, the serum agglutinin of D. affinis showed a distinct and unique specificity for acetyl group-containing carbohydrates and glycoprotein. Furthermore, the hemagglutinating activity of the serum agglutinin was also inhibited by lipopolysaccharide from Salmonella abortus equi, which might indicate a significant role of humoral agglutinin in the immune response of crustaceans against bacterial infection.
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PMID:A lipopolysaccharide-binding hemagglutinin with specificity for acetylated aminosugars in the serum of the hermit crab Diogenes affinis (Henderson). 780 93

To evaluate the cause of the vulnerability to infections in the elderly, the ability of neutrophil to generate reactive oxygen species was assessed by a luminol-dependent chemiluminescence (CL) assay after stimulation with non-opsonized zymosan, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans and lumispheres in elderly patients aged 70 to 93 years. The integrated CL for 20 minutes of whole blood and neutrophils induced by zymosan in the elderly was significantly lower than that in healthy young adults, and the integrated CL of neutrophils induced by lumispheres was also significantly lower in the elderly aged 80 years and over. When bacterial infection occurred in the elderly, the levels of CL were elevated and decreased in the convalescence. This response is proper for host-defense mechanism against infection. However, whole blood CL response was not fully activated in any patients of the elderly during bacterial infection. In these cases lower white blood cell counts, lower neutrophil counts, or the decreased level of the serum total protein, albumin, total cholesterol or cholinesterase were observed. Relationship between malnutrition and the ability of neutrophil to generate reactive oxygen species was suggested. Furthermore, I evaluated the priming effect of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) on whole blood CL. The CL responses stimulated with non-opsonized zymosan or P. aeruginosa were enhanced by pretreatment with TNF-alpha and LPS in healthy young adults. On the other hand, no significant priming effect was observed when blood from elderly patients were incubated with each primer. These findings suggest that the impairment in the generation of reactive oxygen species of the neutrophils and the decrease in reactivity to LPS and TNF-alpha that activate neutrophils at the site of infection and potentiate host defense against invading bacteria, may contribute to susceptibility to infection in the elderly.
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PMID:[Study of neutrophil dysfunctions in the elderly using a chemiluminescence method]. 782 5

Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.
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PMID:Interleukin-10 and the monocyte/macrophage-induced inflammatory response in septic shock. 756 Dec 9

Neonates and leukopenic, immunosuppressed patients are at high risk for severe infection of opportunistic pathogens despite of the availability of potent antimicrobial agents. In this study, antibody titers of immunoglobulin preparations (IVIG) were contrasted with the protective effect in mice against each of bacterial infection. Antibody titers were determined by ELISA. The antigens were 70-80 clinical isolates of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus, respectively. Antibody titers of IVIG against these three gram-negative bacteria ranged 3200 to 102,400. ICR mice were inoculated intraperitoneally with each of several strains against which IVIG showed various titers. IVIG showed rather high protective activities against well-reactive strains, while it showed little protective activities against poor-reactive strains. In the case of P. aeruginosa, statistical analysis of the results obtained with the antibody titer and efficacy showed a good correlation (p < 0.01). On the other hand, IVIG showed a high and complicate antibody titer against S. aureus IVIG ranging 400,000 to 12,800,000, since apparent titers contained non-specific binding of Fc portion of IgG with protein A on the cell wall. IVIG was active in mice, where protein A was less and specific binding was stronger. Bacterial cells have various components; lipopolysaccharide, lipid A, capsule, flagella, pill, etc. that are responsive to specific antibodies. This study indicates that IVIG have such antibodies and that is associated with protective activity against bacterial infection in proportion to antibody titer.
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PMID:[Protective effect and antibody titer of intravenous immunoglobulin (IVIG) against clinical isolates of opportunistic bacteria]. 786 37

Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (i.v.) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline i.v. at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/mL). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P = .013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P = .046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P = .19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P = .032).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of a recombinant endotoxin neutralizing protein in rabbits with Escherichia coli sepsis. 801 61

An experimental disseminated intravascular coagulation (DIC) was induced in female CD rats by the intravenous administration of living bacteria (9.5 x 10(7) cfu Klebsiella pneumoniae), sublethal (5 mg/kg) or lethal (50 mg/kg) lipopolysaccharide (LPS), or tissue factor (1.5 micrograms/kg i.v. bolus or 0.4 micrograms/kg x hr i.v. infusion). We used a new fibrin monomer (FM) assay to follow the course of DIC. FM were detected by their ability to stimulate the tissue-type (t-PA) plasminogen activator dependent conversion of plasminogen to plasmin by a chromogenic assay. Miniplasminogen was used instead of plasminogen to avoid interference of the assay by alpha 2-antiplasmin. As a marker of DIC, elevated levels of FM were observed with all DIC-inducing agents (plasma levels were up to 90 micrograms/ml). The kinetics of FM formation were similar to the course of thrombin-antithrombin III (TAT) levels (maximal plasma levels 70 ng/ml); however, in the bacterial infection group, both parameters rose after a lag phase of about 1 hr. A 4 hr infusion of the highly specific thrombin inhibitor recombinant (rec.) hirudin (0.125 mg/kg x hr) resulted in a decrease of FM levels from 89.2 +/- 14.4 micrograms/ml in the LPS group (n = 10) to 27.4 +/- 11.2 micrograms/ml in the rec. hirudin group (n = 10; P < 0.001). The respective values for TAT levels were 73.1 +/- 19.7 micrograms/ml in the LPS group and 52.7 +/- 15.7 ng/ml in the rec. hirudin group (P < 0.001). Other coagulation parameters, such as platelets, fibrinogen, and fibrin(ogen) degradation products, were ameliorated accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin. 805 64


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