Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P (SP) is an undecapeptide with neurotransmitter and immunoregulatory properties. In murine schistosomiasis, ova naturally induce liver and intestinal granulomas. These granulomas contain macrophages, and eosinophils that produce SP. A report showed that human blood monocytes isolated by adherence release interleukin-1 (IL-1) in response to SP (Lotz et al. (1989) Science 241, 1218). IL-1 is important for initiation of hypersensitivity granulomas. Therefore, it was determined whether SP modulates granuloma macrophage IL-1 production in murine schistosomiasis. Macrophages were obtained from lung and liver granulomas, and from spleens of infected mice. A thymocyte proliferation assay measured IL-1 activity in culture supernatants. Total RNA, extracted from macrophages, was assayed for IL-1 alpha and beta mRNA by Northern blotting using cDNA probes. In response to lipopolysaccharide (LPS), splenic macrophages and macrophages from young lung granulomas released appreciable IL-1. Macrophages from liver granulomas, that were lesions older than the lung granulomas, were unresponsive to LPS with regard to IL-1 secretion. Yet, granuloma macrophages spontaneously expressed IL-1 alpha and beta mRNA. LPS enhanced IL-1 mRNA expression in both splenic and granuloma macrophages. Exposure of macrophages from all sources to SP did not alter IL-1 secretion or gene expression. Similarly, the responsiveness of macrophages to LPS was not affected by concomitant exposure to SP. It is concluded that, in the murine system, SP does not directly influence splenic or granuloma macrophage IL-1 secretion or gene expression. Also, it appears that macrophage secretion of IL-1 is rapidly down-regulated following granuloma elicitation.
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PMID:Substance P does not alter interleukin-1 expression by splenic or granuloma macrophages in murine schistosomiasis. 171 19

Activities of IL-1 produced by peripheral blood monocytes stimulated with lipopolysaccharide and IL-2 released by peripheral blood mononuclear cells induced by PHA, SWAP and SEA in vitro were detected in patients with various stages of schistosomiasis japonica. It was found that the activity of IL-1 was greatly increased and positively related to the body temperature, and high level of IL-2 was induced by SWAP and SEA in the group of acute schistosomiasis. The activity of IL-1 was significantly reduced in the groups of chronic and advanced schistosomiasis, especially in the latter group. The level of IL-2 induced by SWAP and SEA in the groups of chronic and advanced schistosomiasis was significantly lower than that in the group of acute schistosomiasis, but was much higher than that in the group of normal control. The level of IL-2 induced by SWAP and SEA in the cases of acute schistosomiasis was positively related to the activity of IL-1. The results indicate that the specific cellular immunity was increased in acute cases and decreased in chronic cases of schistosomiasis japonica. Both specific and nonspecific cellular immune responses were greatly reduced in cases of advanced schistosomiasis japonica. IL-1 and IL-2 may play an important role in the immunoregulation of schistosomiasis japonica.
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PMID:[Changes in induced interleukin-1 and interleukin-2 activity and their interrelationship in patients with schistosomiasis japonica]. 217 63

Three groups of C57BL/6J female mice were infected with female Schistosoma mansoni cercariae alone, male cercariae alone, or both sexes of cercariae. In a longitudinal study, the spleen cell proliferative responses to the mitogens phytohaemagglutinin (PHA) and Escherichia coli lipopolysaccharide (LPS) were monitored. Significant immune suppression was found in the three infected groups when compared with uninfected controls. Within the infected groups, mice inoculated with both sexes of cercariae were significantly more suppressed than those with single-sex cercarial infection. Thus, in addition to schistosome eggs, either sex of S. mansoni worms is capable, although to a lesser extent, of inducing hyporesponsiveness of cell-mediated immunity (CMI) in chronic schistosomiasis mansoni.
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PMID:Modulation of cell-mediated immunity in mice with chronic unisexual or bisexual Schistosoma mansoni cercarial infection. 251 65

Splenocytes from 25 patients with severe hepatosplenic schistosomiasis mansoni were obtained after therapeutic splenectomy. Spleen cells were phenotyped and analysed for responsiveness to mitogens or heterogeneous schistosome-derived antigenic preparations (eggs, SEA; adult worms, SWAP; cercariae, CERC) in blastogenesis assays and lymphokine production systems, and were compared with peripheral blood mononuclear cells (PBMN). Splenic lymphocytes were 55% T lymphocytes (sheep erythrocyte rosette-positive) and 37% surface immunoglobulin-positive B lymphocytes. The mean T4+:T8+ ratio of these splenocytes was 1.0. Phytohaemagglutinin stimulated spleen cell production of the lymphokine mitogenic factor, but exposure to SEA or SWAP did not. Spleen cell and PBMN blastogenic responses to SEA and SWAP were sometimes, but not always in accord. Removal of plastic adherent cells allowed the non-adherent spleen cells of 30-40% of the patients to respond substantially more vigorously to SEA, SWAP and CERC. Spleen cells from a subgroup of 20-30% of the patients failed to respond to the schistosomal antigens regardless of removal of adherent cells. Spleen cell responses to gram-negative lipopolysaccharide peaked on day 5 or 6 of culture, and were augmented by adherent cell removal. Pokeweek mitogen-stimulated responses were optimal on day 5 of culture. Spleen cells from most severe, hepatosplenic schistosomiasis mansoni patients do not respond well to schistosomal antigens or B-cell mitogens. The splenic responses of many of these patients were elevated by the removal of adherent spleen cells.
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PMID:Immune responses during human schistosomiasis mansoni. XIII. Immunological status of spleen cells from hospital patients with hepatosplenic disease. 309 36

Administration of an antifibrotic agent as an adjunct to antihelmintic treatment with the objective of morbidity reduction was investigated in the murine schistosomiasis mansoni model. Antifibrotic, beta-aminopropionitrile treatment has a profound effect on the cellular matrix composition of the liver granuloma of Schistosoma mansoni infected mice when given alone, resulting in increase macrophage infiltration. These macrophages, in response to stimulation with soluble egg antigen or lipopolysaccharide produced elevated levels of nitric oxide but low levels of tumor necrosis factor alpha compared to untreated infected mice. This also correlated with reduced liver granuloma size. In spite of low numbers of eggs in the liver, mice receiving a combine treatment had a high level of resistance to a challenge infection compared with mice receiving only praziquantel. Those mice also exhibited a reduced lymphocyte proliferative response, similar to that of infected untreated mice. Antifibrotic treatment has an impact on the dynamic of the cellular nature of granulomas and impacts on the host immunity of infection.
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PMID:Impact of antifibrotic treatment of the course of Schistosoma mansoni infection in murine model. 956 41

Nitric oxide (NO) is an extremely important and versatile messenger in biological systems. It has been identified as a cytotoxic factor in the immune system, presenting anti- or pro-inflammatory properties under different circumstances. In murine monocytes and macrophages, stimuli by cytokines or lipopolysaccharide (LPS) are necessary for inducing the immunologic isoform of the enzyme responsible for the high-output production of NO, nitric oxide synthase (iNOS). With respect to human cells, however, LPS seems not to stimulate NO production in the same way. Addressing this issue, we demonstrate here that peripheral blood mononuclear cells (PBMC) obtained from schistosomiasis-infected patients and cultivated with parasite antigens in the in vitro granuloma (IVG) reaction produced more nitrite in the absence of LPS. Thus, LPS-induced nitrite levels are easily detectable, although lower than those detected only with antigenic stimulation. Concomitant addition of LPS and L-N-arginine methyl ester (L-NAME) restored the ability to produce detectable levels of nitrite, which had been lost with L-NAME treatment. In addition, LPS caused a mild decrease of the IVG reaction and its association with L-NAME was responsible for reversal of the L-NAME-exacerbating effect on the IVG reaction. These results show that LPS alone is not as good an NO inducer in human cells as it is in rodent cells or cell lines. Moreover, they provide evidence for interactions between LPS and NO inhibitors that require further investigation.
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PMID:Antigenic stimulation is more efficient than LPS in inducing nitric oxide production by human mononuclear cells on the in vitro granuloma reaction in schistosomiasis. 1055 46

Monocyte tissue factor expression was evaluated in 67 patients with hepatosplenic Schistosomiasis. They were classified as Child A (n = 15), Child B (n = 15), Child C (n = 12) and Bleeders (n = 10), in addition to 15 healthy controls. Mononuclear cells were cultured in vitro with and without lipopolysaccharide (LPS) to assess monocyte tissue factor (TF) antigen (Ag) and activity (Act) in cell lysate, in addition to measurement of prothrombin fragment 1 + 2 (F1 + 2) as a marker of in vivo thrombin generation. A significant increase in monocyte TF Ag and TF Act was noted in all stages of the disease compared with the control group, with marked accentuation during an acute attack of variceal bleeding. This enhanced monocyte expression was noted before the addition of LPS and became more obvious with addition of LPS. An increasing level of F1 + 2 was similarly noted. These findings constitute further evidence for an existing prothrombotic state in hepatosplenic Schistosomiasis, and also that monocytes are closely implicated in the haemostatic diathesis characterizing the disease.
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PMID:Enhanced monocyte tissue factor expression in hepatosplenic schistosomiasis. 1199 66

To study the effect of repeated challenge of the innate immune system with pathogen-associated molecular patterns, cytokine responses to schistosomal lipids and bacterial lipopolysaccharide (LPS) were analyzed in schoolchildren living in an area in Gabon where schistosomiasis, a helminth infection that is chronic in nature, is endemic. A schistosomal phosphatidylserine (PS) fraction containing the Toll-like receptor (TLR)-2 ligand lyso-PS stimulated the production of interleukin (IL)-8, IL-10, IL-6, and tumor necrosis factor (TNF)-alpha in children without Schistosoma haematobium infection. However, in infected children, the responses to this stimulus were lower, in particular for production of IL-8 and TNF-alpha. Responses to the TLR4 ligand, LPS, followed a similar pattern. In contrast, schistosomal adult worm glycolipids that did not stimulate any of the TLRs tested induced IL-8 and IL-6 responses that were significantly higher in schistosome-infected children than in schistosome-uninfected children. These results indicate that relentless exposure to pathogens can lead to altered responses to TLR ligands.
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PMID:Responses to Toll-like receptor ligands in children living in areas where schistosome infections are endemic. 1499 8

In recently exposed communities, intensity of schistosomiasis infection increases as children age and then drops again in adulthood, indicating that host maturity is an important aspect of resistance to schistosomiasis. We investigated whether the cellular immune response to the parasite was correlated with age in subjects with similar daily patterns of exposure, current intensities of infection and number of years of exposure. The cellular immune response of subjects with either 'low' (under 200 eggs per gram (EPG)) or 'high' (over 400 EPG) intensities of infection was investigated, in a recently established focus where subjects had similar histories of exposure and number of years of experience with Schistosoma mansoni. Subject's whole blood was cultured with adult worm antigen (AWA), a mixture of phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), or left unstimulated, and culture supernatants were tested for IL-4, IL-5, IL-10 and IFN-gamma. Children and adults tended to respond differently to schistosome antigen. The most statistically significant illustration of this was the negative correlation between age and IL-5 produced by samples from people with low intensities of infection cultured with AWA (P < 0.003, P < 0.05 after Bonferroni correction). IL-10 produced by samples cultured with PHA and LPS was also notably lower in children than in adults, although not formally significant after Bonferroni correction. This indicates that it is possible for age, independently of intensity of infection or experience with the parasite, to influence the immune response to schistosomiasis.
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PMID:Are the cellular immune responses of children and adults with Schistosoma mansoni infection intrinsically different? Cytokines produced ex vivo in response to antigens and mitogens. 1519 43

Mansonic schistosomiasis remains a medical-social issue in Northeastern Brazil. In children, surgical treatment includes splenectomy and spleen autoimplantation. This procedure reduces post-splenectomy sepsis. The aim of this study was to analyze the phagocyte rate and the cellular viability of monocytes in patients with hepatosplenic schistosomiasis, who underwent splenectomy and spleen autoimplantation from 1991 to 2001. Of the 22 individuals analyzed, 11 were patients who underwent splenectomy and spleen autoimplantation (Study group) and 11 were healthy individuals from the same region (Control group). Both groups presented similar mean age. No difference was found in the phagocyte rate between the control group (36.1%+/-4.9%) and study group (33.5%+/-5.7%). However, phagocyte viability after stimulation with lipopolysaccharide was higher (94%) in control group, when compared to the study group (65%), p<0.001. It is possible to hypothesize that monocytes from the study group patients presented a reduced response to the microorganism challenge, in the face of a harmful and long-lasting stimulus.
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PMID:[Phagocytes rate and cellular viability of the monocytes in patients with hepatosplenic schistosomiasis mansoni who underwent splenectomy and auto-implantation of spleen tissue]. 1716 Mar 20


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