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 effects of representatives of three classes of compounds were investigated on antigen-induced bronchopulmonary eosinophilia in sensitized Brown-Norway rats. Rats were sensitized by 3 weekly inhalation provocations with aerosols of ovalbumin. Twenty-four hours after a fourth weekly antigen provocation, cell populations were enumerated following bronchoalveolar lavage (BAL) in animals treated with test compounds or the appropriate vehicle. A marked eosinophil-rich influx of inflammatory cells into the bronchial lumen followed the antigen provocation in sensitized animals. Dose-related inhibitions of antigen-induced lung eosinophilia were demonstrated with: 1) glucocorticoids, given po (methylprednisolone acetate, U-8210) or by inhalation (methylprednisolone suleptanate, U-67590A); 2)the non-glucocorticoid 21-amino steroid, U-75412E, and 3) the leukotriene B4 antagonist, U-75302. The steroids methylprednisolone and U-75412E were tested for glucocorticoid activity using phorbol ester-differentiated U937 (human macrophage) cells. Methylprednisolone but not U-75412E produced a dose-dependent inhibition of lipopolysaccharide-stimulated thromboxane synthesis by the U937 cells. Leukotriene B4 antagonists and the novel 21-aminosteroid, U-75412E, which lacks glucorticoid activity, provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.
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PMID:Novel inhibitors of pulmonary eosinophil accumulation. 166 9

Mice treated from birth with polyclonal, crude or affinity purified rabbit or monoclonal rat anti-mouse IgM antibodies [b-7-6 and C-2-23: Eur. J. Immunol. 14: 753-757, 1984] were found to be heavily suppressed with respect to B-cell activities. Crude or affinity purified rabbit or monoclonal rat anti-mouse IgM gave comparable results as follows: serum IgM was below detectable levels; serum IgG was reduced to about 1-3% of normal levels; free anti-IgM was always detectable; IgM and/or kappa-light-chain positive cells as well as IgM-secreting cells were absent in various lymphoid organs; the B-cell mitogen lipopolysaccharide was unable to induce proliferative responses; primary antibody responses could not be induced against sheep red blood cells and phosphorylcholine; lymphoid organs were reduced in size and B-cell areas were not populated with lymphocytes; besides a 40% reduction in absolute lymphocyte numbers in the blood, we found increased platelet counts and a 10% eosinophilia in anti-IgM-treated mice.
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PMID:Suppression of B cell development and antibody responses in mice with polyclonal rabbit and monoclonal rat anti-IgM antibodies. I. Characterization of the suppressed state. 390 82

The immunological changes occurring after primary and challenge infections with Strongyloides ratti in C57B1/6 mice are described. Serum IgM and IgG antibodies against Strongyloides antigen appeared one week after primary infection. The levels of antibody in both immunoglobulin classes increased markedly after secondary infection and persisted for at least 6 weeks. Immediate hypersensitivity (15 min footpad) reactions were transient after a primary infection, but were marked and persistent after a secondary infection. Arthus (5 h footpad) reactions were mild and very transient after a primary infection, but a persistent anamnestic response was seen after challenge infection. Cell-mediated immune (24 h footpad) reactions were marked 1 week after both primary and secondary infections but were not sustained in either case. Antigen-reactive cells were present in the mesenteric lymph nodes 1 week after primary infection and 1-4 weeks after challenge infection. No antigen-reactive cells were noted in the spleen. Mesenteric lymph node (MLN) cells and spleen cells from infected or uninfected animals were stimulated with phytohaemagglutinin (PHA) or lipopolysaccharide (LPS) but did not differ significantly in their 3H thymidine incorporation. A transient eosinophilia was observed after primary infection and an anamnestic response was noted after challenge infection. The possible roles of these immunological responses to worm rejection and immunopathology are considered.
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PMID:Humoral and cell-mediated immune responses in murine strongyloidiasis. 717 66

We have determined the inhibitory activity of dexamethasone as an inhibitor of histamine-induced plasma protein extravasation (PPE) in guinea-pig lung and skin, and of lipopolysaccharide (LPS)-induced neutrophilia and platelet activating factor (PAF)-induced eosinophilia in guinea-pig lungs. Dexamethasone inhibited PAF-induced eosinophilia in guinea-pig lung (ED50 1.4 mg/kg i.p.). Higher doses of dexamethasone were required to inhibit LPS-induced neutrophilia (ED50 10.8 mg/kg i.p.). However, at doses up to 150 mg/kg i.p. dexamethasone did not inhibit histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, but did inhibit PPE in guinea-pig skin. These preparations have previously been shown to be equally sensitive to inhibition by the beta 2-adrenoceptor agonist salmeterol. Dexamethasone inhibited PAF-induced eosinophilia (5 mg/kg) or LPS-induced neutrophilia (50 mg/kg) when given 3 h or 1 h prior to challenge. Inhibitory activity was lost when dexamethasone was administered 23 h prior to LPS or 1 h after PAF. The glucocorticoid antagonist mifepristone (1-100 mg/kg i.p.) caused dose-related inhibition of PAF-induced eosinophilia but not of LPS-induced neutrophilia. The highest dose of mifepristone used (100 mg/kg) did not reverse the inhibitory actions of dexamethasone (50 mg/kg) on LPS-induced neutrophilia. We suggest that the different inhibitory activity of dexamethasone in the preparations studied indicates differences in the sensitivity of the target cells involved to inhibition by dexamethasone. We also suggest that inhibition of PAF-induced eosinophilia by mifepristone reflects the partial agonist activity of this agent, demonstrated by others in different experimental systems.
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PMID:Inhibition of some aspects of acute inflammation of guinea-pig lung by intraperitoneal dexamethasone and mifepristone: demonstration of agonist activity of mifepristone in the guinea-pig. 755 78

Eosinophils are supposed to play a critical role in the pathology of several allergic diseases because after activation they can release toxic and proinflammatory agents. In this study we have investigated whether IgE-mediated rat pleurisy could be affected by an ongoing pleural eosinophilic inflammatory response. IgE-passively sensitized rats were challenged with an intrapleural (i.pl.) injection of allergen (dinitrophenylated bovine serum albumin, 1 microgram/cavity) and exudation assessed by measuring the amount of protein extravasated into the pleural cavity within 4 h. We have confirmed that lipopolysaccharide (LPS) stimulation (250 ng/cavity i.pl.) was followed by a marked pleural neutrophilia, apparent at 3 h, which was followed by an eosinophil accumulation noted within 48-72 h postchallenge. We have also confirmed that a boiled sample of LPS pleural washing (LPS-PW, 200 microliters i.pl.) caused selective eosinophilia in recipient rats. Pleural exudation remained unaltered when the allergenic challenge was performed 3 h after LPS in a condition of intense pleural fluid neutrophilia. In contrast, this was significantly reduced (P < .001) when the challenge occurred 72 h after LPS or 24 h after LPS-PW in selective pleural fluid eosinophilia. In another series of experiments repeated daily i.pl. injections of platelet-activating factor (PAF; 1 microgram/cavity) resulted in a progressive increase in eosinophil number recovered from the pleural cavity. The values were 1.2 +/- 0.2, 3.0 +/- 0.2, and 5.8 +/- 0.5 x 10(6) eosinophils/cavity (mean +/- SEM) after 0, 1, and 4 injections, respectively. Allergen challenge performed after 0, 1, or 4 PAF stimulations led to pleural protein levels of 88.6 +/- 5.7, 33.7 +/- 0.7, and 19.4 +/- 2.3 mg/cavity, respectively, indicating that the allergic pleurisy is inhibited in a manner dependent on the magnitude of eosinophil accumulation. Furthermore, the impairment of PAF-induced eosinophil accumulation by cetirizine (30 mg/kg i.p.) restored the exudatory response. Exudation triggered by compound 48/80 (25 micrograms/cavity), histamine (200 micrograms/cavity), or 5-hydroxytryptamine (100 micrograms/cavity) was not affected by four previous PAF daily injections. The findings indicate that allergen-induced exudation is selectively down-regulated in the eosinophil-enriched pleural space of rats, a suppression that increased with increasing eosinophil number and disappeared after chemical impairment of the eosinophilia.
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PMID:Pleural fluid eosinophils suppress local IgE-mediated protein exudation in rats. 756 15

In this study we investigated the involvement of inflammatory cells in the pleural accumulation of eosinophils induced by lipopolysaccharide (LPS). Intrathoracic (i.t.) injection of LPS (250 ng/cavity) into rats induced a significant eosinophil accumulation that developed within 24 h, was maximal at 48 h, and returned to control values within 120 h. This eosinophil influx was preceded by a huge neutrophil influx within 4 h and accompanied by a mononuclear cell accumulation between 24 and 48 h. Pretreatment with an antineutrophil monoclonal antibody (RP-3, 2 ml per animal) selectively reduced the number of circulating neutrophils within 8 h but failed to alter the LPS-induced eosinophilia. Similarly, platelet depletion with an anti-rat platelet antiserum did not alter the LPS-induced eosinophil accumulation. Cyclosporine (50 mg/kg, 12 and 2 h before) partially inhibited (51%) the LPS-induced pleural eosinophilia, whereas the eosinophilia was not changed by prior degranulation of pleural mast cells with polymyxin B (10 micrograms/cavity, 24 h before). Moreover, selective depletion of T lymphocytes using an anti-Thy 1.0 monoclonal antibody significantly inhibited the eosinophilia triggered by LPS. The i.t. injection of liposomes containing dichloromethylene diphosphonate significantly reduced (65%) the number of resident macrophages after 5 days. Under this condition, the eosinophil infiltration induced by LPS was completely inhibited. Accordingly, the i.t. injection of supernatant from macrophage monolayers, obtained from the pleural cavities of LPS-injected rats, into naive recipient animals led to a twofold increase in the number of pleural eosinophils. In conclusion, our data suggest an important role for resident macrophages and T lymphocytes in the eosinophil accumulation induced by LPS.
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PMID:Requirement for lymphocytes and resident macrophages in LPS-induced pleural eosinophil accumulation. 807 92

Intrathoracic injection of endotoxin lipopolysaccharide, LPS into rats induced a dose-dependent increase in the number of eosinophils recovered from the pleural cavity. The pleural eosinophil accumulation peaked within 24-48 h, and returned to basal levels within 120 h. This phenomenon was accompanied by mononuclear cell infiltration, and preceded by massive neutrophil accumulation. Pretreatment with indomethacin, BW 755C (a dual cyclo/lipoxygenase inhibitor), BW A4C (a specific lipoxygenase inhibitor) or the platelet activating factor (PAF) antagonists WEB 2086 and PCA 4248 failed to inhibit the endotoxin-induced pleural eosinophilia, whilst dexamethasone (5-10 micrograms/cavity) or cycloheximide (14-28 micrograms/cavity) abolished this phenomenon. Transfer of the cell-free pleural washing from LPS-treated donor rats to normal recipient rats led to a two-fold increase in the eosinophil counts. Treatment of donors, but not recipients, with cycloheximide or dexamethasone inhibited the eosinophil accumulation induced by the pleural washings, indicating that the generation of the eosinophilotactic activity, but not its effects, depends on protein synthesis. This eosinophilotactic activity was maintained after lyophilization and heating (100 degrees C for 30 min), but was destroyed by trypsin. This substance has a molecular weight ranging between 10 and 50 kDa. The available data suggest that the late eosinophil accumulation induced by LPS is independent of arachidonic acid metabolites and PAF, and probably depends on a newly generated heat-stable soluble protein.
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PMID:Pharmacological modulation of lipopolysaccharide-induced pleural eosinophilia in the rat; a role for a newly generated protein. 833 53

Due to the inhibition of 5-lipoxygenase-activating protein (FLAP), BAY x1005 is a new selective inhibitor of leukotriene synthesis. The effects of BAY x1005 on the antigen- and bacterial lipopolysaccharide (LPS)-induced airway hyperresponsiveness in guinea pigs were investigated. Six times provocation of aeroantigen caused biphasic increases in airway resistance which peaked at 1 hr (immediate phase reaction) and 4 hrs (late phase reaction). It also caused airway hyperreactivity to acetylcholine. BAY x1005 at doses of 10 mg/kg and 30 mg/kg significantly inhibited antigen-induced increase in respiratory resistance (Rrs) at 1 and 4 hrs after the last antigen challenge. Simultaneously, BAY x1005 inhibited the antigen-induced airway hyperresponsiveness at doses of 10 and 30 mg/kg and airway eosinophilia (bronchoalveolar lavage study) at a dose of 30 mg/kg. In addition, BAY x1005 at a dose of 30 mg/kg inhibited bacterial LPS-induced airway hyperreactivity to acetylcholine. In this model, BAY x1005 did not affect the increase of the number of leukocytes in bronchoalveolar lavage fluid. These results suggest that BAY x1005 is a potent anti-asthmatic agent with an inhibitory action to airway hyperreactivity.
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PMID:Effect of a novel leukotoriene synthesis inhibitor, BAY x1005, on the antigen-and LPS-induced airway hyperresponsiveness in guinea pigs. 871 Nov 35

The potency of dexamethasone has been determined as an inhibitor of intratracheally administered platelet activating factor- (PAF), or interleukin (IL)-5-induced eosinophilia, and of lipopolysaccharide-(LPS), tumour necrosis factor alpha-(TNF alpha) or cytokine-induced neutrophil chemoattractant- (CINC) induced neutrophilia in guinea-pig lungs. Dexamethasone was a potent inhibitor of PAF- induced eosinophil accumulation, but higher doses of dexamethasone were required to inhibit IL-5-induced eosinophilia. LPS-induced neutrophilia was less sensitive to the inhibitory effects of dexamethasone, than PAF-induced eosinophilia. Both LPS- and TNF alpha-induced neutrophilia were inhibited by the same doses of dexamethasone. In contrast, higher doses of dexamethasone were required to inhibit CINC-induced neutrophilia. Since data in the literature show that PAF-induced eosinophilia in guinea-pig lungs is dependent on the generation of IL-5, it is concluded that inhibition of this response, by dexamethasone, is due to inhibition of release of IL-5. Similarly, although data in the literature show that LPS-induced neutrophilia is dependent on the generation of TNF alpha, it is concluded that inhibition of this response, by glucocorticoids, is due to an action on an event which occurs after the release of TNF alpha, possibly through inhibition of chemokine release.
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PMID:Inhibition of PAF-, LPS-, and cytokine-induced granulocyte accumulation in guinea pig lung by dexamethasone: evidence that inhibition of IL-5 release is responsible for the selective inhibition of eosinophilia by glucocorticoids in guinea-pigs. 874 Oct 5

New world nonhuman primates of the genus Aotus (owl monkeys) can be categorized by 11 distinct karyotypes (K). It has been demonstrated that monkeys of K-VI persistently have one order of magnitude more eosinophils (EOS) in the peripheral blood than K-I monkeys. The purpose of this study was to investigate the basis for this difference and examine EOS recruitment using two cutaneous models of inflammation. Peripheral blood EOS were isolated on metrizamide gradients to > or = 95% purity and then used for phenotypic studies. There were no significant differences when comparing karyotypes in the ratio of normodense (K-I, 6.4% +/- 3.8%; K-VI, 21.1% +/- 8.8%) EOS or their survival in culture (K-I, 5.3% +/- 2.9% at 72 hours; K-VI, 2.8% +/- 0.7% at 72 hours) (P > .05). Examination of bone marrow revealed that K-VI monkeys had greater than fivefold more EOS and EOS precursors than K-I animals. To examine EOS function in recruitment, monkeys of each karyotype were given a single intradermal injection of Escherichia coli lipopolysaccharide (LPS) or human recombinant (PMN) and mononuclear cells occurred in response to LPS as early as 4 hours after injection; the severity of infiltration was similar in both karyotypes and at all time points up to 24 hours. In contrast, by 8 hours after intradermal injection of RANTES, leukocyte infiltration in K-I monkeys consisted mostly of PMN (94.8% +/- 0.7%) that were predominantly EOS. In comparison, there was essentially no infiltrate in K-VI animals at all time points. There was no difference in VCAM-1 expression in response to intradermal LPS or RANTES between the two karyotypes. These results suggest that the genetic basis of peripheralblood eosinophilia in K-VI owl monkeys is likely a function of heightened eosinophilopoiesis and depressed recruitment kinetics from the peripheral circulatory pool in response to RANTES.
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PMID:Peripheral blood eosinophilia in owl monkeys is associated with increased eosinophilopoiesis yet depressed recruitment kinetics to the Chemokine RANTES. 882 74


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