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 sulphasalazine (SASP), sulphapyridine (SP), and 5-aminosalicylic acid (5-ASA) have been studied on mouse spleen cells cultured in the presence of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). SASP exhibited a significant degree of suppression, at doses in the range 25-100 micrograms/ml (p less than 0.01), this suppression being greater than 50% at 50 micrograms/ml. SP exhibited only a minor degree of suppression (10% at 75 micrograms/ml, p less than 0.01). Coadministration of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, produced no evidence of further suppression in the presence of SASP or SP. Administration of SP plus 5-ASA to parallel cultures that were profoundly suppressed by the molecular equivalent amount of SASP resulted in no suppression. This implied requirement of the intact parent molecule (SASP) to produce this effect, at these concentrations. The concentration of SASP required to produce more than 50% suppression was higher than that ever attained in the peripheral blood of humans receiving therapeutic doses of the drug. Human lymphocytes are similarly suppressed by SASP, but only at higher concentrations than are required for murine cells. Thus, if the parent drug is the active moiety and requires these concentrations to be effective in vivo, it follows that the site where these effects may be mediated is likely to be the intestinal tract. The effects described would suggest the gut associated lymphoid tissue as a likely target.
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PMID:Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes--clues to its clinical action? 290 97

Much evidence suggests that Peyer's patch (PP) lymphocytes are capable of mounting both humoral and cell-mediated immune responses to luminal antigenic stimuli. To shed further light on T-T and T-B cell interactions in gut mucosal immune-associated processes, we studied in vitro the effects of a variety of PP-derived concanavalin A (Con A)-activated immunoregulatory T-cell subsets on class-specific immunoglobulin (Ig) production by lipopolysaccharide (LPS)-activated PP-derived B cells. Particular attention was focused on induction of a contrasuppressor T-cell immunoregulatory network in the above in vitro system. Three types of immunoregulatory effector T cells, a helper T (Th) cell, a suppressor T (Ts) cell and a contrasuppressor T (Tcs) cell were developed and isolated. The results showed that B cell Ig production was under the regulation of these T cells, and the L3T4+ Lyt-2- T cell, which bound to Vicia villosa (VV), had a contrasuppressor effector function. In addition, a L3T4+ Lyt-2- VV- Ts inducer (Tsi) subset and a L3T4- Lyt-2+ VV- Ts effector subset also appeared to participate in the sequential development of the suppressor and, probably, contrasuppressor immunoregulatory networks, respectively. Thus, PP T cells are likely to execute their highly sophisticated immunoregulatory functions, not only in the helper and suppressor circuits but also in the contrasuppressor circuit in response to intraluminal non-specific stimuli. However, IgA isotype-specific Ig production appears to be controlled primarily by the isotype-specific helper circuit, not by the contrasuppressor circuit, in polyclonal LPS-stimulated gut mucosal immune responses.
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PMID:In vitro induction of a contrasuppressor immunoregulatory network by polyclonally activated T cells derived from murine Peyer's patches. 296 98

Human milk is a suspension of viable cells. Macrophages are the most abundant cells, comprising 40-80% of the total cell count. The present study was initiated to examine the principal cell functions of phagocytic milk macrophages: adherence, chemotaxis and phagocytosis-associated bactericidal oxidative metabolism. Adherence of milk macrophages to nylon wool was significantly decreased when compared with blood monocytes. In addition chemotaxis of macrophages in response to C 5a or a synthetic chemotactic peptide was also decreased. However, macrophages produced oxygen intermediates (O2-), H2O2) to a similar extent as blood monocytes after stimulation of the "oxidative burst" with phorbol myristate acetate or opsonized Candida particles. Macrophages cultured in vitro in endotoxin-free medium without serum lost the ability to produce oxygen metabolites over the course of a few days. Partial restoration of the oxygen radical production could be detected in macrophages exposed to bacterial lipopolysaccharide, i.e. endotoxin (LPS, 10 ng/ml). Endotoxin, which is present in the gut even of newborns might provide enough stimulation to maintain macrophages in the "primed" state. We conclude that oxygen metabolites released from milk macrophages are highly reactive and could contribute essentially to the protection of neonates against microbial infections.
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PMID:[Function of breast milk macrophages]. 300 13

Plasma lipopolysaccharide (LPS) concentrations have been found to increase during a temporary occlusion of the superior mesenteric artery (SMA). We have attempted to show, by a prophylactic oral administration of a nonabsorbable antibiotic to monkeys subjected to an SMA occlusion shock, that the increased LPS is intestinal in origin. A total of eight monkeys were subjected to a temporary occlusion of the SMA. Four monkeys received prophylactic oral administration of a nonabsorbable antibiotic, while the rest acted as controls. The plasma LPS concentrations before occlusion in the control and the kanamycin group were 0.069 +/- 0.006 and 0.092 +/- 0.005 ng/ml, respectively. At the end of the 1-hr occlusion period the plasma LPS concentration in the controls increased to 0.09 +/- 0.009 ng/ml (P less than 0.1) and peaked to 0.378 +/- 0.103 ng/ml (P less than .001) within 20 min of reperfusion. Thereafter, the plasma LPS concentration returned slowly to baseline. In the kanamycin group the plasma LPS concentration remained at baseline throughout both the occlusion and reperfusion periods. These data suggest that the origin of the increased plasma LPS concentration seen following temporary occlusion of the SMA is from the gut, and is information of possible importance in patients about to undergo intestinal surgery.
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PMID:Oral administered nonabsorbable antibiotics prevent endotoxemia in primates following intestinal ischemia. 304 8

Cytokines are proteins produced mainly by lymphocytes in response to an antigenic stimulus. Originally identified and named on the basis of their biological activity, they are now called interleukins; together with the interferons, colony-stimulating factors and tumour necrosis factor/cachectin (TNF) they form a complex and overlapping network of communication between immunocompetent cells. Cytokines play a central role in T cell activation, and interleukin 2 and interferon gamma in particular are involved in the expression of graft-versus-host disease after bone marrow transplantation. Recent studies suggest that TNF is also implicated: the gene encoding TNF is situated close to the MHC gene in both mice and humans, and TNF is able to up-regulate constitutively expressed class II antigen and, with interferon gamma, to induce class II expression in previously normal cells. Bacterial lipopolysaccharide (endotoxin) is a powerful stimulus to TNF, and TNF production may be the mechanism underlying the longstanding observations on the role of the bacterial microflora of the gut in graft-versus-host disease.
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PMID:Cytokines as mediators of graft-versus-host disease. 304 86

A number of disease states and therapeutic maneuvers common to surgical patients can result in changes in the intestinal flora, permitting bacterial overgrowth and translocation of bacteria to gut lymphoid tissue. It is possible that these changes in gut flora increase portal levels of several factors that are capable of altering macrophage activation state, including endotoxin, lymphokines, and eicosanoids. Since Kupffer cells are directly exposed to gut factors via the portal circulation, changes in intestinal flora may influence Kupffer cell responses. Using germfree rats, it has previously been shown that the presence of gut bacterial flora is important in inducing Kupffer cells to respond to endotoxin, and that an overgrowth of gram-negative bacteria can further augment Kupffer cell responses, supporting the above-mentioned hypothesis. The current set of experiments examines how intestinal gram-negative bacterial overgrowth in normal adult rats effects the response of Kupffer cells to septic stimuli. Kupffer cells were obtained from conventional rats with induced intestinal overgrowth with Escherichia coli C25 for 2 or 7 days. After 2 days of overgrowth, Kupffer cells were only slightly less responsive to lipopolysaccharide (LPS) than control Kupffer cells. However, after 7 days of overgrowth, when placed in coculture with normal hepatocytes, Kupffer cells were significantly more responsive to LPS (p less than 0.001), inducing a greater degree of suppression in hepatocyte protein synthesis at lower LPS concentrations. When cultured alone, Kupffer cells from these animals also produced more interleukin-1 (p less than 0.002) and prostaglandin E2 (PGE2) (p less than 0.009) in response to LPS. These results show that intestinal gram-negative bacterial overgrowth in conventional rats can have direct influences on the response of hepatic macrophages to septic stimuli, and provides further support to the hypothesis that imbalances in the intestinal flora can effect the responses of immune cells in other sites of the body.
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PMID:Intestinal gram-negative bacterial overgrowth in vivo augments the in vitro response of Kupffer cells to endotoxin. 305 29

Antiserum to Escherichia coli J5, a mutant endotoxin (LPS) which contains only core determinants, has proven effective in reducing mortality from endotoxic shock due to a wide variety of gram-negative bacteria. Twenty New Zealand white rabbits with coliforms in the gut were subjected to hemorrhagic shock of 36 mm Hg for 3 hr. Treated rabbits were resuscitated with 15 cc of rabbit J5 antiserum (hemagglutinating antibody titer against J5 lipopolysaccharide of 1:1024), remaining shed blood, and lactated Ringer's to achieve a mean arterial blood pressure (MABP) within 20% of baseline. The control group was similarly resuscitated but received 15 cc normal rabbit serum (titer 1:2). Catheters were removed and rabbits were returned to their cages until death or 5 days of survival. Hemodynamic parameters (heart rate, MABP, cardiac output, and total peripheral resistance) did not differ significantly between groups. However, six treated rabbits survived 5 days (60%) and no control rabbit lived past the third postexperimental day (P less than 0.019). Our data suggest that systemic endotoxemia may contribute to morbidity and mortality in severe hemorrhagic shock.
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PMID:Antiserum to endotoxin in hemorrhagic shock. 305 23

The formation of antibodies against lipopolysaccharide in the mouse after daily administration of 10(10) killed Escherichia coli M17 (serotype 02:K1) was studied. An IgA response in gut is already established at the first day after an immunization period of 5 days. The kinetics of antibody formation in gut lavage fluid and bile are similar. In comparison lipopolysaccharide-specific IgG antibodies against lipopolysaccharide in serum are raised later.
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PMID:[Lipopolysaccharide-specific antibodies in intestinal lavage fluid, bile and serum of mice after oral application of inactivated Escherichia coli]. 307 74

To study presumptive diarrhoeagenic and invasive properties of Plesiomonas shigelloides, adult conditioned rabbits (n = 75) were fed 10(10) CFU of 3 isolates (2 from diarrhoea patients and one from river water) of the organism, and one isolate of Shigella sonnei (from a dysentery patient as positive control) or brain-heart infusion broth (as negative control). Each rabbit received in succession i.v. cimetidine (50 mg/kg body weight), two 15 ml oral doses of 5% NaHCO3 at 15 and 30 minutes respectively, prompt bacterial or sham inoculum followed 30 minutes by 2 ml of i.p. tincture of opium. Rabbits fed with P. shigelloides did not die or develop diarrhoea, but in a majority of them, histopathological examinations of the intestine revealed mild acute inflammation of the mucosa, mainly in the ileum. There was no serum antibody response by indirect haemagglutination against the lipopolysaccharide of the homologous strains of P. shigelloides. The culture filtrates of the organism also did not show any cytotoxic morphological changes on CHO and Y1 adrenal cell cultures. By contrast, rabbits fed with S. sonnei developed clinical diarrhoea, small to widespread severe acute inflammation of the gut mucosa, and all died on day 7. It may be concluded that P. shigelloides are able to provoke a mild inflammatory lesions of the gut mucosa in this rabbit model; but there is little prospect of using this model to assess easily the virulence of the organism.
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PMID:Enteropathogenicity of plesiomonas shigelloides by oral inoculation in adult conditioned rabbits. 327 Apr 56

We examined whether infection with enterotoxigenic Escherichia coli (ETEC) producing the heat-labile enterotoxin (LT) can prime the gut immune system to respond more efficiently to the immunologically related cholera B subunit component of a recently developed oral B subunit-whole-cell cholera vaccine (B-WCV). Nine Bangladeshi adults who had been hospitalized for watery diarrhea caused by LT-producing ETEC were given a single oral immunization with B-WCV on day 28 after hospital admission. The vaccine preparation used was adjusted to contain a lower-than-usual dose of B subunit, which had been found in previous studies to elicit a significant gut mucosal immunoglobulin A antitoxin response mainly in individuals with previous toxin-specific priming of their gut immune system. For comparison, nine patients convalescing from severe cholera disease and eight healthy subjects with no recent history of either cholera or ETEC infection were given the same oral vaccination with B-WCV. Vaccination in the ETEC convalescents induced an immunoglobulin A antitoxin response in intestinal lavage fluid which was comparable with that in the vaccinated cholera convalescents and superior to that in the vaccinated, previously uninfected controls. By contrast, only the cholera patients responded with anamnestic-type anti-cholera lipopolysaccharide antibody titer rises in the intestine after vaccination. These data support the specificity of the anamnestic anti-cholera toxin response in the ETEC patients after vaccination with cholera B-WCV.
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PMID:Enterotoxigenic Escherichia coli diarrhea in an endemic area prepares the intestine for an anamnestic immunoglobulin A antitoxin response to oral cholera B subunit vaccination. 327 84


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