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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2-) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min-1 kg-1). 2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy. 3. O2- generation by isolated monocytes was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2- production was significantly (P = 0.008) higher for non-survivors (31.3 +/- 8.8 nmol 30 min-1 10(-6) cells; n = 4) than for survivors (6.2 +/- 2.3 nmol 30 min-1 10(-6) cells; n = 7). 4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2- production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2- production with opsonized zymosan. 5. These results suggest that (1) increased O2- production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2- production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.
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PMID:Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep. 166 89

Endotoxin (lipopolysaccharide, LPS) can induce shock, multiple organ failure, and death. A recombinant N-terminal fragment of bactericidal/permeability increasing protein, rBPI23, binds with high affinity to gram-negative bacterial LPS and neutralizes its biological activity. We sought to determine the effect of rBPI23 on LPS-induced respiratory dysfunction and cardiovascular depression in conscious rabbits. Rabbits were injected with Escherichia coli O113 LPS (6 micrograms/kg) and treated with rBPI23 (2 mg/kg), vehicle, or control protein after recovery from surgery performed to implant catheters for hemodynamic assessments and intravenous injections. LPS challenge caused respiratory dysfunction including tachypnea, significant decreases in arterial O2 tension (PO2), arterial oxygen content, and an increase in alveolar-arterial O2 gradient (A-aDO2). LPS administration also resulted in profound and prolonged decreases in mean arterial blood pressure and cardiac index. Treatment with rBPI23 prevented LPS-induced respiratory dysfunction and significantly ameliorated the cardiovascular depression. 5 of 16 LPS-challenged animals died of respiratory failure and acidosis, whereas none died in the rBPI23 treated group (p = .11). The results demonstrate that rBPI23 protects animals against LPS-induced cardiopulmonary depression in endotoxic shock.
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PMID:Protective effects of a recombinant N-terminal fragment of bactericidal/permeability increasing protein on endotoxic shock in conscious rabbits. 774 57

Alveolar macrophages (AM), which represent the major resident population of immunocompetent cells in the lower respiratory tract, have been implicated in the pathogenesis of acute lung injury in view of their exceptional capacity to release a large array of inflammatory mediators. The ex vivo analysis of these cells, accessible to bronchoalveolar lavage (BAL) is hampered by the fact that, under conditions of respiratory failure, the AM pool is heavily expanded by polymorphonuclear neutrophils (PMN), which necessitates separation of these cell populations. In the present study, we describe a flow cytometric approach to sort human AM obtained from BAL samples of both healthy volunteers (n = 10) and patients with severe pneumonia demanding mechanical ventilation (n = 10), using forward scatter and high autofluorescence characteristics to discriminate AM from PMN and lymphocytes. This technique yielded highly purified AM populations (>95%) as evidenced by morphological analysis, cytochemistry, and CD71 and CD14 expression of the sorted cells. The flow sorting process, per se, did not induce the expression of the acute-phase cytokine tumor necrosis factor-alpha (TNF-alpha) in control AM as determined by reverse transcriptase-polymerase chain reaction. Unstimulated and lipopolysaccharide-induced TNF-alpha protein secretion were comparable in sorted and unsorted AM as demonstrated by enzyme-linked immunosorbent assay. We suggest flow sorting of viable human AM as an efficient and nonperturbing separation technique to yield highly purified cell populations especially from PMN-rich BAL fluids of critically ill patients.
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PMID:Separation of human alveolar macrophages by flow cytometry. 912 15

Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.
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PMID:Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats. 925 46

Group B streptococci (GBS) are a major cause of severe infection in newborns, pregnant females, and other immunocompromised hosts. Infection often includes septicemia, shock, pneumonia, and respiratory failure. In previous studies, we have reported that GBS induce marked production of tumor necrosis factor alpha (TNF-alpha) by human mononuclear cells. The present study was designed to measure the production of TNF-alpha as well as additional cytokines, including interleukin 1beta (IL-1beta), IL-6, IL-8, IL-12, and gamma interferon (IFN-gamma) but also to determine from what cells and at what time point during incubation with GBS that these cytokines are produced. Mixed mononuclear cells were incubated with heat-killed GBS, media alone, or 1 microg of Escherichia coli lipopolysaccharide (LPS). Brefeldin A was added to each sample prior to staining, which prevented the export of cytokines by the Golgi apparatus. The cells were then stained with the appropriate conjugated antibodies and analyzed by using a flow cytometer. Results indicate that intracellular cytokines appear, in almost all cases, simultaneous to or before secreted proteins are detected. In contrast to the response to LPS, where TNF-alpha, IL-1beta, IL-6, and IL-8 appear almost simultaneously, the human monocyte response to GBS results in the production of TNF-alpha but delayed appearance of IL-1beta, IL-6, and IL-8. The lymphocyte response to GBS was also strikingly different from that to LPS in that both secreted IFN-gamma and IL-12 was detected, while LPS failed to induce production of these critical cytokines. This suggests an important role for TNF-alpha, IFN-gamma, and IL-12 in GBS pathogenesis and/or immunity.
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PMID:Intracellular and extracellular cytokine production by human mixed mononuclear cells in response to group B streptococci. 1060 4

The correlation of clinical and immunological parameters with the duration of respiratory failure was investigated to identify factors determining the clinical outcome of respiratory syncytial virus (RSV) bronchiolitis necessitating mechanical ventilation. At initiation of mechanical ventilation in 30 patients with RSV, production of interleukin (IL)-12 and IL-10 was measured in 48-h peripheral blood cell cultures that were stimulated with lipopolysaccharide and interferon-gamma. The ventilation index (VI)-an indicator of respiratory dysfunction that includes partial pressure of arterial CO2, peak airway pressure, and respiratory rate-correlated with the duration of mechanical ventilation (r=.47; P=.013). Age was not associated with the duration of mechanical ventilation. A highly significant inverse correlation was found between the duration of mechanical ventilation and the production of IL-12 at admission (r=-.62; P<.001). This correlation was independent of VI. No correlation was found between IL-10 production and the duration of mechanical ventilation. It is hypothesized that low monocyte IL-12 response during initial RSV infection adversely affects clinical outcome of patients with severe RSV bronchiolitis.
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PMID:Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis. 1082 82

Adult respiratory distress syndrome (ARDS) is characterized by acute lung injury with a high mortality rate and yet its mechanism is poorly understood. Sepsis syndrome and acid aspiration are the most frequent causes of ARDS, leading to increased lung permeability, enhanced polymorphonuclear neutrophil (PMN) sequestration and respiratory failure. Using a murine model of acute lung injury induced by septic syndrome or acid aspiration, we investigated the role of cytosolic phospholipase A2 (cPLA2) in ARDS. We found that disruption of the gene encoding cPLA2 significantly reduced pulmonary edema, PMN sequestration and deterioration of gas exchange caused by lipopolysaccharide and zymosan administration. Acute lung injury induced by acid aspiration was similarly reduced in mice with a disrupted cpla2 gene. Our observations suggest that cPLA2 is a mediator of acute lung injury induced by sepsis syndrome or acid aspiration. Thus, the inhibition of cPLA2-initiated pathways may provide a therapeutic approach to acute lung injury, for which no pharmaceutical agents are currently effective.
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PMID:Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. 1088 Nov 66

Group B streptococci (GBS) are important pathogens in neonatal sepsis and pneumonia. GBS stimulate alveolar macrophages to produce inflammatory cytokines and free oxygen radicals, which can damage the lungs. In several studies, use of exogenous surfactant in term babies has improved outcome related to sepsis and respiratory failure. The role(s) of exogenous surfactant in modulating the inflammatory response produced by this microbe was examined. Tumor necrosis factor alpha (TNF-alpha) production and luminol-enhanced chemiluminescence (LCL), a measure of respiratory burst, were investigated. For measuring TNF-alpha release, RAW 264.7 murine macrophages were pre-incubated with bovine surfactant and stimulated with either lipopolysaccharide, live or heat-killed GBS type Ia. LCL was measured after macrophages were pre-incubated with or without surfactant overnight, then stimulated with GBS or phorbol myristate acetate. Lipopolysaccharide and GBS stimulated TNF-alpha secretion from macrophages that was suppressed by exogenous surfactant in a dose-dependent fashion. GBS and phorbol myristate acetate also increased LCL from macrophages, which was significantly suppressed by pre-incubation of macrophages with exogenous surfactant. We conclude that GBS type Ia stimulates TNF-alpha release and LCL from RAW 264.7 cells and that these responses are suppressed by surfactant. Suppression of inflammatory mediators by exogenous surfactant might improve respiratory disease associated with GBS.
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PMID:Immunomodulation by exogenous surfactant: effect on TNF-alpha secretion and luminol-enhanced chemiluminescence activity by murine macrophages stimulated with group B streptococci. 1133 43

Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in the development of CLD. Steroids have been shown to produce some improvement in neonates with this disease. The purpose of this study was to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the clinical benefit of steroids in babies. Our results showed that dexamethasone, budesonide and rIL-10 significantly inhibited both IL-6 and TNF-alpha production in the THP-1 cell line stimulated by lipopolysaccharide and Ureaplasma urealyticum antigen. Similar effects were found in macrophages from tracheobronchial aspirate fluid from newborn infants. In the rat alveolar macrophage cell line, steroids inhibited IL-6 and TNF-alpha production, while rat rIL-10 did not significantly decrease production. In conclusion, steroids and human rIL-10 were able to downregulate proinflammatory cytokine production, which may explain the beneficial effect of steroids and suggests that rIL-10 could be tried as an anti-inflammatory agent in neonates with a high risk of CLD.
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PMID:Inhibition of macrophage proinflammatory cytokine expression by steroids and recombinant IL-10. 1150 12

Lung injury in preterm neonates with respiratory failure has been attributed to persistent inflammation, which is likely to involve lung macrophages (LM). The study objective was to investigate LM during the first 8 d of life from preterm infants (n = 19), using term infants (n = 11) with respiratory failure as control subjects. LM percentages from mixed-cell suspensions produced from tracheobronchial lavage were calculated. A postnatal increase in the mean LM concentration was demonstrated within the preterm group (p = 0.01), which was greater in comparison to that from the term group (p < 0.01). Regression analyses were significant for direct relationships between LM concentrations and ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha and IL-10 production (r = 0.93 and r = 0.63, respectively), establishing LM as the source of these cytokines. Comparative analyses demonstrated that the ability of preterm versus term LM to produce tumor necrosis factor-alpha was nearly identical; in contrast, a trend toward diminished levels of IL-10 expression in the preterm group was observed (p = 0.06). Thus, although studies have shown that LM precursors (i.e. cord blood monocytes) produce less tumor necrosis factor-alpha in preterm versus term infants, the present data strongly suggest that this relationship does not hold postnatally with respect to terminally differentiated LM in sick neonates. Overall, the data are consistent with a pro- versus antiinflammatory imbalance that may bear functional significance on the pathogenesis of chronic lung disease.
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PMID:Lipopolysaccharide-induced tumor necrosis factor-alpha and IL-10 production by lung macrophages from preterm and term neonates. 1172 31


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