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)

Endotoxemia results in neutrophil localization within a number of microcirculatory beds, reflecting in part an adhesive interaction between neutrophils and the vascular endothelial cell. In previous studies, endotoxin or lipopolysaccharide (LPS) treatment of rabbits resulted in neutrophil sequestration at LPS concentrations well below those effective at increasing neutrophil adherence in vitro. We hypothesized that LPS-induced neutrophil adherence involved a plasma component. In the absence of plasma, high concentrations of LPS (10 micrograms/ml) were required to increase human neutrophil adherence to endothelial cells in vitro. With the inclusion of as little as 1% plasma or serum, however, the LPS dose-response curve was markedly shifted, resulting in increments in adherence at 10 ng/ml, and the time course of enhanced adherence was accelerated. Pretreatment studies suggested that the effect of LPS was on the neutrophil rather than the endothelial cell. Immunoprecipitation of 0111:B4 LPS paralleled the loss of functional activity, suggesting that LPS was an integral part of the active complex, rather than altering a plasma component to make it active. The incubation of plasma with LPS decreased the apparent molecular mass of LPS from 500-1,000 kD to approximately 100 kD. The disaggregated 0111:B4 LPS eluted in the range of albumin and was able to increase adherence in the absence of additional plasma. Plasma depleted of lipoproteins or heat treated retained activity, suggesting that the interaction of LPS with HDL or complement did not account for the observed findings. An LPS-binding protein isolated from rabbit serum enhanced the adherence-inducing effects of both 0111:B4 and Re595 LPS. Furthermore, the activity of rabbit serum was abolished after incubation with an antibody directed against this LPS-binding protein (LBP). An antibody directed against CD14, the putative receptor of the LPS-LBP complex, prevented the adhesive response to LPS. These data suggest that LPS is disaggregated by an LBP in serum and plasma to form an active LPS-plasma component complex. This putative complex then interacts with CD14 on the neutrophil so as to induce an adhesive state.
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PMID:Neutrophil adherence induced by lipopolysaccharide in vitro. Role of plasma component interaction with lipopolysaccharide. 128 37

We investigated whether human granulosa-luteal (GL) cells exhibited lipopolysaccharide (LPS)-binding protein, and the response of follicular aspirate cells to LPS in vitro. Follicular aspirates taken from a human in-vitro fertilization and gamete intra-fallopian-tube transfer programme were subjected to Percoll gradients in order to isolate an enriched population of GL cells. GL cells exhibited specific LPS-binding protein, detected by autoradiography of the cellular lysate on SDS-PAGE after the cells were specifically labelled with a radioiodinated, photoactivable and reducible LPS derivative. LPS binding to the cells was also detected by the appearance of immunofluorescence associated with the cellular membrane when incubated with a fluorescent conjugated LPS receptor antibody. Ninety-four per cent of the cells exhibiting immunofluorescent LPS-binding protein were also positive for the steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase, as detected by cytochemistry. In order to detect a response to LPS, the enriched population of GL cells were cultured in vitro in the presence or absence of LPS; after 16 h of culture, tumour necrosis factor-alpha (TNF) mRNA was detected by reverse transcription-polymerase chain reaction and Southern blot analysis of the amplified cDNA. The expression of TNF mRNA was enhanced when the cells were cultured in the presence of LPS, which also significantly enhanced TNF secretion into the media during the 16-h period. These results reveal that GL cells exhibit LPS-binding protein and thus increased TNF secretion occurs in response to LPS in follicular aspirate cells. The source of ovarian TNF may be leukocytes, macrophages and/or GL cells.
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PMID:Evidence for lipopolysaccharide binding in human granulosa-luteal cells. 128 78

We measured intracytoplasmic free calcium ion concentration ([Ca3+]i) of alveolar macrophages (AMs) in order to elucidate the mechanism(s) of lipopolysaccharide (LPS)-hyperresponsiveness of AMs in patients with sarcoidosis at the second messenger level. Resting [Ca2+]i was higher in patients with sarcoidosis than in normal subjects. [Ca2+]i increase responses were also elevated in patients with sarcoidosis when AMs were stimulated with either anti-CD14 (a LPS/LPS-binding protein complex receptor) antibody, anti-CD64 (Fc gamma receptor I), antibody or platelet activating factor. After incubation with interferon-gamma, resting [Ca2+]i and increase in [Ca2+]i induced by anti-CD14 antibody stimulation were higher in patients with sarcoidosis as compared with values before incubation. Thus, these data suggest that activation of AMs at the second messenger level induced by IFN gamma, at least in part, accounts for LPS-hyperresponsiveness in sarcoidosis.
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PMID:[Alveolar macrophages and granuloma formation]. 128 54

Previous research in this laboratory, using photoactivatable radioiodinated lipopolysaccharide derivatized with sulfosuccinimidyl-2-(p-azidosalicylamide)-1,3'-dithiopropionate (125I-ASD-LPS), has resulted in the identification of a specific LPS receptor with a molecular mass of approximately 73 kDa on murine lymphocytes and splenic macrophages. The experiments presented in this report investigated whether a similar LPS-binding protein was also expressed on human peripheral blood populations, including monocytes, lymphocytes, neutrophils, platelets, and erythrocytes. Each cell population was incubated with 125I-ASD-LPS, UV irradiated, washed, reduced, and solubilized, and the cell lysates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. On all of the cell populations, except erythrocytes, a similar 73-kDa LPS-binding protein was present. In addition, each population also expressed lower-molecular-weight secondary LPS-binding proteins, some of which were conserved among the populations. Binding of the photoactivatable LPS probe was found to be both time and temperature dependent. These data support the concept that the 73-kDa LPS-binding protein is conserved on multiple cell types from a variety of species.
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PMID:Identification and characterization of lipopolysaccharide-binding proteins on human peripheral blood cell populations. 137 70

Luminol-enhanced chemiluminescence was used to determine the effect of soluble CD14 (sCD14) on the endotoxin-inducible generation of reactive oxygen species in human monocytes. It was necessary to mediate lipopolysaccharide (LPS) monocyte-activating capability by serum factors (LPS-binding proteins). sCD14 reduced LPS-inducible monocyte activation in a dose-dependent manner, even in the case of CD14- monocytes, obtained from a patient with paroxysmal nocturnal haemoglobinuria. These monocytes could be activated by opsonized LPS via other receptors. Using anti-mouse Ig-coated microbeads, it was demonstrated in FACS analysis that sCD14 mediates the binding of a mouse monoclonal anti-CD14 antibody (RoMo 1) to a complex of LPS/FITC (fluoroisothiocyanate) and a LPS-binding protein. The release of sCD14 from cultured monocytes was measured using LPS, TNF alpha (tumour necrosis factor), IL1, 4 and 6 (interleukin-1, -4 and -6) and IFN gamma (interferon-gamma) as stimulators. Addition of LPS and TNF alpha led to a dose-dependent increase in sCD14-levels in the culture supernatant, whereas IL1, IL6 and IFN gamma had no significant effect. IL4 dose-dependently depressed spontaneous sCD14 release. It is possible that elevated sCD14-serum levels in polytraumatized patients indicate a natural protective mechanism against excessive monocyte mediator production. Therefore, sCD14 may be a new therapeutic concept in endotoxic shock prevention.
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PMID:Endotoxin-neutralizing capacity of soluble CD14. 137 13

The monocyte is a pivotal cell in septic patients that responds to endotoxin with release of inflammatory cytokines. Monocytes display on their surface a receptor (CD14) for complexes formed by endotoxin (lipopolysaccharide, LPS) and a plasma LPS-binding protein (LBP). We compared monocytes obtained from normal controls with those obtained from septic patients for expression of CD14 by flow cytometric analysis of immunofluorescent-stained cells. In normal individuals and patients, 75%-95% of monocytes are CD14 positive (CD14+). Mean fluorescence exhibited by the CD14+ population was measured after maintaining cells at 37 degrees C for 15 minutes and compared with baseline cells held at 4 degrees C (mean fluorescence ratio). All cells increased their CD14 mean fluorescence ratio with warming; however, the level achieved by monocytes obtained from septic patients was on average 78% +/- 8% of control levels (p = 0.014). To further clarify CD14 expression, we examined the effect of Escherichia coli LPS on normal monocytes by comparing monocytes treated in serum-free buffer (no LBP) with monocytes treated in whole blood (containing LBP). The LPS (1.0 ng/mL) incubated with whole blood for 120 minutes generated an increase in CD14+ mean fluorescence compared with buffer. In contrast, phorbol myristate acetate lowered CD14+ mean fluorescence levels. These data indicate that normal monocytes incubated in the presence of ligand (LBP-LPS complexes) increase their expression of CD14, whereas CD14 expression in septic patients is diminished. We conclude that monocytes from septic patients were responsive to other stimuli aside from LPS and that decreased expression of CD14 may indicate a poor prognosis.
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PMID:Modulation of the endotoxin receptor (CD14) in septic patients. 137 77

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens. 137 54

Only recently has the mechanism for lipopolysaccharide (LPS) recognition by macrophages been elucidated. In contrast to many ligand receptor interactions, the interaction of LPS with its receptor, CD14, on myeloid cells is greatly enhanced by prior complexation of LPS with LPS-binding protein (LBP), a recently discovered plasma glycoprotein. LBP is found in normal serum or plasma in the 5 to 10 micrograms/ml range. In plasma, it reacts rapidly but transiently with LPS. LPS-LBP complexes then react with CD14 bearing cells. Blocking CD14 with monoclonal antibodies or removal of LBP from plasma blocks the ability of the cells to react with LPS-LBP complexes and also blocks release of cytokines and other mediators from the cells. In the normal lung, bronchoalveolar lavage fluid contains low levels of LBP. However, during acute lung injury, LBP levels may rise by transudation and enhance activation of alveolar macrophages to release injurious mediators. Description of this pathway for LPS recognition by macrophages and other leukocytes offers the possibility of developing new reagents to block LPS recognition and prevent the development of endotoxemia.
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PMID:Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation. 138 94

Recently it has been demonstrated that the CD14 molecule which is expressed on monocytes and macrophages serves as a receptor for lipopolysaccharide (LPS) bound to LPS-binding protein (LBP) and thus mediates LPS-induced tumour necrosis factor (TNF) production. Here we report that CD14 is found as a soluble (s) molecule in serum. In healthy volunteers sCD14 levels (mean +/- s.e.m.) were 3.7 +/- 0.05 micrograms/ml (n = 30, 25-50 years of age) as determined by ELISA (detection limit 20 ng/ml serum) using two monoclonal antibodies in a sandwich technique. In polytraumatized patients (n = 16) significantly decreased levels (1.7 +/- 0.3) were detected immediately after the trauma, which increased to 4.9 +/- 0.3 micrograms/ml within the first 6 days post trauma. sCD14 remained elevated during the first 14 days post trauma in patients with the most severe injuries (injury severity score greater than 45 points), whereas a return to normal levels was observed in patients with an injury score of less than 45 points. In addition, the levels of the high-density lipoproteins that partially inactivate free endotoxin are significantly decreased post trauma. No correlation between parameters of inflammation (C3a and neopterin levels, leucocyte counts, amount of band cells), liver function and sCD14 levels was established. Comparable to polytraumatized patients, increased sCD14 serum levels were observed in five patients with burn trauma (burned area greater than 35%) within the second week post trauma when clinical signs of septicaemia were evident.
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PMID:Serum CD14 levels in polytraumatized and severely burned patients. 171 13

During Gram-negative endotoxemia, precise regulation of monocyte/macrophage (M phi) responsiveness to lipopolysaccharide (LPS) is critical to preserve host defense while avoiding complications such as organ failure and death. We will discuss regulation of LPS-M phi interactions by LPS-binding plasma proteins and by LPS-induced changes in M phi responsiveness. Upon exposure to plasma, LPS binds to either lipoproteins or LPS-binding protein (LBP; a 60-kilodalton glycoprotein with a high-affinity binding site for the lipid A moiety of rough and smooth LPS). The LPS-LBP complex stimulates the M phi by binding to its cellular receptor, CD14 (a monocyte/M phi-specific, phosphatidylinositol-anchored surface glycoprotein). Pretreatment of whole blood with anti-CD 14 monoclonal antibody reduces the responsiveness of monocytes to LPS [determined by tumor necrosis factor-alpha (TNF-alpha) release]at least 10-fold. Similarly, cellular responsiveness to LPS is diminished at least 100-fold by depletion of plasma LBP with anti-LBP antibody. Compared to LPS-LBP induction of TNF-alpha, LPS-lipoprotein complexes are as much as 10,000-fold less active. Thus, partitioning of LPS between LBP and lipoproteins markedly influences M phi responsiveness to LPS. LPS also directly induces M phi hyporesponsiveness to itself by a process known as adaptation; exposure of M phi to less than or equal to LPS/ml (subthreshold for TNF induction) for 6-9 reduces the sensitivity of the M phi to subsequent challenge up to 1,000-fold, so that 1 microgram/ml rather than 1 ng/ml of LPS is required for maximal induction of TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory mechanisms of host responsiveness to endotoxin (lipopolysaccharide). 188 13


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