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 therapeutic effects of an intravenously injected carboxamide derivative (IS-741) on lung injury were studied in rats with cerulein-induced pancreatitis complicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a challenge of endotoxemia. Rats were divided into four groups: group I, pancreatitis with LPS; group II, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 was administered 30 min before the endotoxemia challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats with LPS (group I), but hemorrhage was not seen in group IV rats receiving a continuous injection of IS-741 shortly before the induction of endotoxemia. The IS-741-treated rats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). The number of neutrophils infiltrating the lung in groups II, III, and IV was significantly lower than that of group I. Conversely, CINC production by bronchoalveolar macrophages in vitro were stimulated by LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectively prevented pancreatitis-associated lung injury following the challenge of endotoxemia.
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PMID:Novel carboxamide derivative (IS-741) attenuates lung injury in rats with cerulein-induced pancreatitis complicated by endotoxemia. 1006 21

Cytokines play a pivotal role in the pathogenesis of septic shock. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) stimulate the progression of septic shock whereas the anti-inflammatory cytokine IL-10 has counterregulative potency. The amino acid glycine (GLY) has been shown to protect against endotoxin shock in the rat by inhibiting TNF-alpha production. In the current study we investigated the role of GLY on lipopolysaccharide (LPS) -induced cell surface marker expression, phagocytosis, and cytokine production on purified monocytes from healthy donors. GLY did not modulate the expression of HLA-DR and CD64 on monocytes, whereas CD11b/CD18 expression (P<0.05) and E. coli phagocytosis (P<0.05) decreased significantly. GLY decreased LPS-induced TNF-alpha production (P<0.01) and increased IL-10 expression of purified monocytes. Similarly, in a whole blood assay, GLY reduced TNF-alpha (P<0.0001) and IL-1beta (P<0.0001) synthesis and increased IL-10 expression (P<0.05) in a dose-dependent manner. The inhibitory effects of GLY were neutralized by strychnine, and the production of IL-10 and TNF-alpha was augmented by anti-IL-10 antibodies. Furthermore, GLY decreased the amount of IL-1beta and TNF-alpha-specific mRNA. Our data indicate that GLY has a potential to be used as an additional immunomodulatory tool in the early phase of sepsis and in different pathophysiological situations related to hypoxia and reperfusion.
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PMID:Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression. 1006 24

In rat models of Gram-negative pneumonia, pulmonary emigration of neutrophils (polymorphonuclear leukocytes [PMNs]) is blocked when rats are made endotoxemic by an intravenous administration of endotoxin (lipopolysaccharide [LPS]). To test whether dysfunctional PMN migratory responses in the endotoxemic rat are specific for airway endotoxin, we gave rats intrapulmonary stimuli known to elicit different adhesion pathways for pulmonary PMN migration. Sprague-Dawley rats were treated intravenously with either saline or LPS and then instilled intratracheally with either sterile saline, LPS from Escherichia coli, interleukin (IL)-1, hydrochloric acid (HCl), zymosan-activated serum (ZAS), or lipoteichoic acid (LTA). Three hours later, accumulation of PMNs and protein in bronchoalveolar lavage fluid (BALF) were assessed. BALF PMN accumulation in response to intratracheal treatment with LPS (100%), IL-1 (100%), ZAS (40%), and LTA (58%) was inhibited by endotoxemia. In rats given intratracheal HCl, BALF PMN numbers were unaffected by intravenous LPS. The pattern of inhibition of migration suggests that intravenous LPS only inhibits migration in response to stimuli for which migration is CD18-dependent. In contrast to PMN migration, BALF protein accumulation was inhibited by intravenous LPS only when IL-1 or LPS was used as the intratracheal stimulus. To characterize further the differential responses to the various airway stimuli, the appearance in BALF of tumor necrosis factor-alpha (TNF-alpha) and the PMN chemokine macrophage inflammatory protein (MIP)-2 was measured. Accumulation of PMNs in BALF correlated with the BALF concentrations of MIP-2 (r = 0.846, P < 0.05) and TNF (r = 0.911; P < 0.05). The ability of intravenous LPS to inhibit pulmonary PMN migration correlated weakly with MIP-2 (r = 0.659; P < 0.05) and with TNF (r = 0.413; P > 0.05) concentrations in BALF. However, this correlation was strengthened for TNF (r = 0.752; P < 0.05) when data from IL-1-treated animals were excluded. Thus, the presence in BALF of inflammatory mediators that are known to promote CD18-mediated migration correlates with endotoxemia-related inhibition of PMN migration. Furthermore, the pattern of inhibition of pulmonary PMN migration during endotoxemia is consistent with the CD18 requirement of each migratory stimulus.
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PMID:Inhibition of pulmonary neutrophil trafficking during endotoxemia is dependent on the stimulus for migration. 1010 Oct 10

Multiple sclerosis (MS) is a central nervous disease thought to be elicited by an autoimmune process. Many studies in recent years have concentrated on finding the alterations in the peripheral blood immune profile in MS patients that would reflect disease activity. In the present study, we investigated surface antigen expression on lymphocytes and granulocytes from MS patients and control subjects. We have studied 29 patients suffering from relapsing-remitting or relapsing-progressive forms of MS. The disease was diagnosed in all patients at least 12 months before inclusion into the study. All patients had no attack at the study entry date or within a previous month. The control group included 29 age-matched subjects. Phenotyping of peripheral blood leukocytes was carried out with different fluorescence-conjugated murine monoclonal antibodies. The analysis was performed with three-color flow cytometry. The following antigens were determined [cluster of definition (CD)]: leukocyte common antigen (LCA) (B220, T 200, Ly-5), CD45; LPS-R (lipopolysaccharide receptor), CD14; found on all T cells, CD3; LFA-2 (lymphocyte function associated antigen, T 11), CD2; coreceptor for MHC class II molecules, found on helper T cells, CD4; coreceptor for MHC class I molecules, found on suppressor/cytotoxic T cells, CD8; B4, found on all human B cells, CD19; NCAM (neural cell adhesion molecule), CD56; integrin beta2 subunit, associated with CD11a (CD11a/CD18, LFA-1, alphaLbeta2) and CD11b (CD11b/CD18, Mac-1,CR3, alphaMbeta2), CD18; alphaL, alpha subunit of integrin LFA-1 (alphaLbeta2, CD11a/CD18), CD11a; alphaM, alpha subunit of integrin Mac-1 (CR3, alphaMbeta2, CD11b/CD18), CD11b; ICAM-1 (intercellular adhesion molecule), CD54; H-CAM, Hermes antigen, Pgp-1, CD44; AIM (activation inducer molecule), early activation antigen, CD69; T-cell receptor gammadelta, TCR gammadelta. In the MS group, we have found a significant increased expression of CD54 and CD44 antigens on lymphocytes, and higher percentage CD54(+) and CD11a+CD54(+) lymphocytes out of all lymphocytes compared with the control group. We have also found a significant increased expression of CD11a, CD18 and CD54 antigens on granulocytes, and higher percentage CD11b+CD18(+) granulocytes out of all granulocytes in MS patients compared with control. Higher levels of expression of the adhesion molecules may reflect the activation state of leukocytes in MS patients.
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PMID:Phenotyping analysis of peripheral blood leukocytes in patients with multiple sclerosis. 1021 Sep 17

The ability of several Pseudomonas aeruginosa exo-enzymes, including exotoxin A (ETA), to induce inflammation and their influence on endotoxin-induced tumour necrosis factor (TNF) production in murine lung were evaluated. Intratracheal administration of lipopolysaccharide (LPS; 0.1-10 microg/mouse), 2(-1) LD50 of P. aeruginosa alkaline protease (7.5 microg/mouse) and elastase (1.2 microg/mouse) elevated total cell number and the percentage of neutrophils in broncho-alveolar lavage fluid (BALF), whereas ETA (0.1 microg/mouse) did not. LPS induced TNF production in BALF in a dose-dependent manner, whereas the P. aeruginosa exo-enzymes did not. When ETA was inoculated into the respiratory tract before LPS, production of TNF in BALF was significantly suppressed in a dose-dependent manner. ETA also suppressed TNF production by alveolar macrophages (AMs) stimulated with LPS in vitro. Flow cytometric analysis showed that ETA markedly reduced the expression of CD14 and CD11c/CD18 on the surface of AMs. ETA also depressed partially the expression of TNF-alpha mRNA in AMs. These findings suggest that ETA regulates TNF production in murine lung by suppressing LPS receptor expression, mRNA expression and protein synthesis and/or secretion of TNF.
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PMID:Effect of Pseudomonas aeruginosa exotoxin A on endotoxin-induced tumour necrosis factor production in murine lung. 1022 44

We investigated the role of platelet-activating factor (PAF) as a priming signal for cytokine-induced neutrophil chemoattractant (CINC) expression by bronchoalveolar macrophages in acute pancreatitis. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-h intervals) in Wistar rats. The animals were injected intraperitoneally with 10 micrograms/kg of lipopolysaccharide (LPS) as a septic challenge. Pancreatitis rats were treated with a bolus intravenous injection of TCV-309 (3 or 30 micrograms/kg) 30 min before the septic challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in pancreatitis rats complicated with sepsis but were not seen in pancreatitis rats receiving a bolus TCV-309. Pancreatitis rats treated with TCV-309 had lower serum concentrations of CINC after septic challenge and lower levels of CINC messenger RNA (mRNA) in the lung, as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). In vitro CINC production in response to LPS by bronchoalveolar macrophages obtained from pancreatitis rats 6 h after the first cerulein injection, immediately before septic challenge, was enhanced but was significantly reduced in a TCV-309-sensitive manner. LPS-stimulated in vitro CINC production by naive bronchoalveolar macrophages was significantly enhanced by pretreatment with PAF. TMB-8 (an inhibitor of calcium release from endoplasmic reticulum) or W7 (calmodulin antagonist) completely abrogated the chemoattractant production by bronchoalveolar macrophages pretreated with PAF after LPS stimulation. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of bronchoalveolar macrophages to release CINC after triggering with LPS during acute cerulein-induced pancreatitis. The PAF antagonist TCV-309 effectively prevented hyperactivity of bronchoalveolar macrophages and pancreatitis-associated lung injury after the septic challenge.
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PMID:Platelet-activating factor antagonist (TCV-309) attenuates the priming effects of bronchoalveolar macrophages in cerulein-induced pancreatitis rats. 1023 40

Preterm infants have an increased incidence of infection, which is principally due to deficiencies in neonatal host defense mechanisms. Monocyte adherence is important in localizing cells at sites of infection and is associated with enhanced antimicrobial functions. We isolated cord blood monocytes from preterm and full-term infants to study their adhesion and immune functions, including superoxide (O2-) generation, degranulation, and cytokine secretion and their adhesion receptors. O2- production and degranulation were significantly diminished, by 28 and 37%, respectively, in adherent monocytes from preterm infants compared to full-term infants (P < 0. 05); however, these differences were not seen in freshly isolated cells. We also observed a significant decrease of 35% in tumor necrosis factor alpha secretion by lipopolysaccharide-stimulated adherent monocytes from preterm infants compared to full-term infants (P < 0.05); however, this difference was not observed in interleukin-1beta or interleukin-6 production by the monocytes. The cell surface expression of the CD11b/CD18 adhesion receptor subunits was significantly decreased (by 60 and 52%, respectively) in monocytes from preterm infants compared to full-term infants (P < 0. 01). The cascade of the immune response to infection involves monocyte upregulation and adherence via CD11b/CD18 receptors followed by cell activation and the release of cytokines and bactericidal products. We speculate that monocyte adherence factors may be important in the modulation of immune responses in preterm infants.
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PMID:Decreased superoxide production, degranulation, tumor necrosis factor alpha secretion, and CD11b/CD18 receptor expression by adherent monocytes from preterm infants. 1039 55

1. The potent coronary vasoconstrictor, endothelin-1 (ET-1) may also regulate neutrophil traffic into tissues. The aim of the present study was to characterize the endothelin receptors responsible and to investigate the underlying mechanisms. 2. ET-1 (1 nM - 1 microM) markedly enhanced attachment of human neutrophils to lipopolysaccharide-, and to a lesser extent, to ET-1-activated human coronary artery endothelial cells (HCAEC). This can partially be blocked by monoclonal antibodies against E-selectin, L-selectin or CD18, whereas combination of the three antibodies inhibited adhesion by approximately 83%. Increases in neutrophil adhesion evoked by ET-1 were also blocked by the platelet-activating factor (PAF) antagonists, BN 52021 (50 microM) and WEB 2086 (10 microM). 3. ET-1 downregulated the expression of L-selectin and upregulated expression of CD11b/CD18 and CD45 on the neutrophil surface and induced gelatinase release with EC50 values of approximately 2 nM. These actions of ET-1 were almost completely prevented by the ET(A) receptor antagonist FR 139317 (1 microM) and the ET(A)/ET(B) receptor antagonist bosentan (10 microM), whereas the ET(B) receptor antagonist BQ 788 (1 microM) had no effect. ET-1 slightly increased the expression of E-selectin and ICAM-1 on HCAEC, that was prevented by BQ 788, but not by FR 139317. 4. Receptor binding studies indicated the presence of ET(B) receptors (KD: 40 pM) on phosphoramidon-treated HCAEC and the predominant expression of ET(A) receptors (KD: 38 pM) on neutrophils. 5. These results indicate that promotion by ET-1 of neutrophil adhesion to HCAEC is predominantly mediated through activation of ET(A) receptors on neutrophils and subsequent generation of PAF.
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PMID:Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET(A) receptors and platelet-activating factor. 1043 5

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.
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PMID:Allergen-stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide. 1044 28

Patients with chronic obstructive lung disorders often show increased susceptibility to airway infections. As beta 2-adrenoceptor agonists, in addition to reversing the contractile response of bronchial smooth muscles, may inhibit a variety of inflammatory and immuno-effector cell functions, it is possible that these drugs interfere with host defence mechanisms. The present study was designed to test in vitro whether fenoterol, a short-acting beta 2-adrenoceptor agonist, could modify human blood neutrophil recruitment and antimicrobial activity. Pre-exposure to fenoterol significantly reduced neutrophil migration towards the complement component C5a, at concentrations ranging from 10(-7) M to 10(-5) M, or towards lipopolysaccharide, at a concentration of 10(-5) M (P < 0.05, each comparison). In contrast, the drug (10(-8)-10(-5) M) did not significantly modify the increased expression of lymphocyte function-associated antigen (LFA-1, i.e. CD11a/CD18) the macrophage antigen-1 (Mac-1, i.e. CD11b/CD18) induced by N-formylmethionylleucylphenylalanine (fMLP) (P > 0.05, each comparison). Finally, incubation of neutrophils with fenoterol (10(-8)-10(-5) M) did not significantly influence phagocytosis or intracellular killing of bacteria (Staphylococcus aureus) or H2O2 release induced by tetradecanoyl-phorbol-acetate (P > 0.1 for each comparison). These results suggest that short-acting beta 2-adrenoceptor agonists, such as fenoterol, are able partially to reduce neutrophil recruitment in the airways without interfering with the processes involved in phagocytic activity against bacteria.
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PMID:beta 2-agonist-induced inhibition of neutrophil chemotaxis is not associated with modification of LFA-1 and Mac-1 expression or with impairment of polymorphonuclear leukocyte antibacterial activity. 1046 25


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