Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms associated with the modulation of immune response in the chronic phase of human schistosomiasis mansoni infection are complex and involve many cell types. In the present paper the authors demonstrate that antigenic stimulation of peripheral blood mononuclear cells (PBMC) from chronic-intestinal schistosomiasis mansoni patients with polyacrylamide beads (PB) conjugated to Schistosoma mansoni soluble egg antigens (PB-SEA) or adult worm antigen preparation (PB-SWAP) were able to induce a statistically significant increase on the in vitro multinucleated giant cell (MGC) formation after the 15th day in culture. A correlation between an increase in the number of MGC and a decrease in in vitro granuloma formation index to PB-SEA and PB-SWAP was observed. Moreover, the authors demonstrated a down-regulation of lymphocyte proliferative responses to S. mansoni antigens, during the differentiation pathway of monocytes towards MGC formation, due to a decrease in the antigen-presenting capacity of these cells. These phenomena also correlate with a concomitant decrease in the expression of HLA-DR and CD54 adhesion molecules on the surface of MGC. The results suggest that differentiation of monocytes to MGC may be one of the immunoregulatory mechanisms involved in the down-regulation of the granuloma reaction against S. mansoni eggs.
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PMID:Human schistosomiasis: modulation of in vitro granulomatous hypersensitivity and lymphocyte proliferative response by macrophages undergoing differentiation. 894 5

Rattus rattus is the predominant rodent in the mangrove area of Guadeloupe. Between 1990 and 1991 we found 73 R. rattus and five R. norvegicus. Among the infected rats with Schistosoma mansoni, 59% for R. rattus and 80% for R. norvegicus, the comparison of the median of the worm load was not statistically different. Both species of infected rats showed adult worms and eggs in the lungs and 20% of them showed, at the same time, two and even three generations of worms. Neither adults nor eggs were seen in the intestinal wall or stools of R. norvegicus, instead R. rattus had eggs in the liver, in the intestinal wall and the stools. Therefore, R. norvegicus gets infection as well as R. rattus, but does not participate in the transmission of the schistosomiasis. In order to elucidate this difference, we looked at the humoral recognition of these two rats, to the molecular antigens of the three stages of the parasite: cercaria, adult worm (AWA) and egg (SEA). In general, R. norvegicus recognized cercarial antigens more frequently than R. rattus, 73, 81 and 172 kDa being statistically different. Regarding AWA, molecules 82, 86, 117 and 150 kDa were recognized more often by R. rattus as compared to R. norvegicus. The reverse was true for the 18, 33 and 61 kDa. Only the differences between 61 and 150 kDa molecules were statistically significant. With respect to SEA, R. norvegicus recognized more 28, 45, 47, 49, 64 and 92 kDa molecules than R. rattus, but the latter recognized the 140 kDa molecules of SEA to a higher degree (95 and 140 kDa were significantly different). It is plausible that the immune response to cercarial invasion is more effective in R. norvegicus in allowing the parasites to reach adulthood, but it does not let them live in the mesenteric veins and therefore to lay their eggs in the intestinal wall and feces.
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PMID:Natural Schistosoma mansoni infection in wild rats from Guadeloupe: parasitological and immunological aspects. 935 99

The present study was designed to explore if there exists a correlation between predominant isotype-defined antibody levels and reinfection in low age groups of the population in an endemic area of schistosomiasis japonica in China. One hundred and thirty-eight individuals aged 3-25 years old were selected for serological investigations including the levels of IgG, IgG4, IgM and IgE, detected by ELISA with soluble egg antigen and soluble adult worm antigen. Results show that age is a determinant for SEA-specific IgG, IgG4, and IgE, and SWA-specific IgG and IgG4 antibody levels, which increased with age, and that SEA- and SWA- specific IgG4 antibody levels are risk factors of reinfection, ie, the risk of reinfection occurrence of the population with high level of SEA or SWA-specific IgG4 is 2.83 or 2.40 times, respectively, that with low level of SEA or SWA-specific IgG4, suggesting that in the endemic area of schistosomiasis japonica, there exists a possibility that in the population aged 3-25 years, SEA and SWA-specific IgG4 antibodies mediate a blocking immunity response.
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PMID:Isotypic antibody responses of a population in an endemic area of schistosomiasis japonica and their epidemiologic significance. 944 4

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-gamma may be associated with resistance to infection.
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PMID:Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection. 968 96

Nitric oxide (NO) is an important effector molecule involved in immune regulation and defense. NO produced by cytokine-activated macrophages was reported to be cytotoxic against the helminth Schistosoma mansoni. Identification and characterization of S. mansoni antigens that can provide protective immunity is crucial for understanding the complex immunoregulatory events that modulate the immune response in schistosomiasis. It is, then, essential to have available defined, purified parasite antigens. Previous work by our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to SEA (soluble egg antigen) or to SWAP. In the present work we report the effect of different in vivo trials with mice on their spleen cells ability to produce NO. We demonstrate that PIII-immunization is able to significantly increase NO production by spleen cells after in vitro stimulation with LPS. These data suggest a possible role for NO on the protective immunity induced by PIII.
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PMID:Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells. 992 44

Periovular granuloma formation during Schistosoma mansoni infection is a complex, multifaceted immunologic response. Products of arachidonic acid metabolism have been shown to contribute to this response through studies in which general inhibitors of lipoxygenase function reduce granulomatous inflammation. To determine which lipoxygenases are important for granuloma development in schistosomiasis, wild type mice or mice deficient for 5-lipoxygenase (5-LO) or "leukocyte-type" 12-lipoxygenase (12-LO) were infected with S. mansoni and studied for responses to schistosome eggs and egg antigens. At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice. 5-LO mice also displayed less antibody-mediated (5 h) and cell-mediated, delayed-type (24 h) hypersensitivity to schistosome egg antigens than did the other two infection groups. In an attempt to determine possible mechanisms for the reduced inflammatory responses, we also measured hepatic mRNA levels of cytokines that have been shown to influence granuloma size (IL-4, IL-10, and IFN-gamma). The mRNA levels for IL-10 were significantly lower in 5-LO-deficient mice, but SEA-stimulated spleen cells did not demonstrate a significant difference in IL-10 production between wild type and 5-LO mice. These data suggest that 5-LO plays a role in host responses to schistosomiasis via a mechanism that cannot be explained solely by changes in expression of these cytokines.
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PMID:Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni. 999 Jun 74

Human resistance and susceptibility to schistosomiasis is associated with age and specific antibody isotype responses against worm (SWAP) and egg (SEA) antigens. In a cross-sectional study of 176 individuals infected with Schistosoma japonicum in the Philippines, strikingly similar isotype response patterns against SWAP and SEA was observed when compared to other endemic areas. Interestingly, IgA titres to SWAP correlated with older age among S. japonicum-infected individuals (n = 176, P < 0.01), suggesting a role for this isotype in protective immunity. To identify the molecular targets of human IgA, 17 high-IgA/SWAP responders were identified from the said population. IgA antibodies from the majority (14/17) of these individuals recognized a band of 97 kDa (Sj97), comigrating in immunoblots with the myofibrillar protein paramyosin. The antigen was confirmed as paramyosin by expressed sequence tag (EST)-analysis of four clones obtained by screening an adult S. japonicum cDNA library with pooled IgA antisera and mouse antiparamyosin polyclonal antibodies. The identification of paramyosin as a major target of human IgA raises its potential as a vaccine candidate that targets mucosal immune responses. Since this antigen is exposed on the parasite surface only during the lung stages, we propose that human IgA contributes to parasite attrition during schistosome migration in the lungs.
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PMID:Paramyosin is a major target of the human IgA response against Schistosoma japonicum. 1058 66

Separation and purification of rSj32 were carried out with SDS-PAGE and electroelution technique. The purified rSj32, AWA and SEA were used to examine sera of patients with schistosomiasis, healthy individuals and patients with other parasitic diseases by ELISA. The results showed that the molecule weight of rSj32 was 37 kD. The sensitivity and specificity of rSj32 as a coating antigen in ELISA were as good as those of AWA and SEA. It is suggested that rSj32 antigen is a potential antigen for immunodiagnosis of schistosomiasis japonica.
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PMID:[Schistosoma japonicum: purification and diagnostic application of recombinant 32 kD antigen]. 1118 85

Antibody isotypic responses (IgE, IgA, IgG1, IgG2, IgG3 and IgG4) to Schistosoma japonicum antigens--adult worm (AWA), soluble egg (SEA) and the recombinant proteins TEG (22.6-kDa tegumental antigen, Sj22) and PMY (paramyosin, Sj97)--were measured (in 1998) in a cohort of 179 Chinese subjects 2 years post-treatment. Subjects in the highest intensity re-infection group (> 100 eggs per gram faeces) had significantly higher levels of IgG1 and IgG4 against AWA. Analysis of IgG4/IgE ratios for AWA and SEA linked IgG4 excess to re-infection and IgE excess to non-re-infection. Two years after chemotherapeutic cure, 29 subjects, who were re-infected or never infected but highly water-exposed, were classified as epidemiologically susceptible (n = 15) or epidemiologically insusceptible to infection (n = 14). IgG4 levels against native antigens (AWA and SEA) were higher in susceptible and IgE levels were higher in insusceptible but antibody responses to the recombinant proteins (PMY and TEG) showed no clear pattern or difference between susceptibility groups. These and earlier findings provide evidence that immunity develops against schistosomiasis japonica in China and that susceptibility/resistance correlates with antibody isotypes against native schistosome antigens.
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PMID:Human susceptibility to Schistosoma japonicum in China correlates with antibody isotypes to native antigens. 1157 93

Activation of protein tyrosine kinases (PTKs) is a common step of T cell stimulation. However, the relationship between PTKs and activation of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients has not been explored yet. In this study, we investigated the participation of Lck and ZAP-70 protein tyrosine kinases (PTKs), as well as PLC-gamma1 and Shc proteins in PBMC activation by Schistosoma mansoni antigens. PBMC were stimulated with SEA (soluble egg antigen) or SWAP (soluble worm preparation), lysed, precipitated with specific antibodies and the level of tyrosine phosphorylation evaluated. Our results show that Lck and Shc were phosphorylated upon stimulation of the cells with SWAP, as well as with SEA. However, the phosphorylation level was more pronounced in SWAP than in SEA-stimulated cells. Phosphorylation of ZAP-70 was observed only in SWAP stimulated cells. Additionally, PLC-gamma1 phosphorylation was not observed in PBMC stimulated with SEA. Together, these results indicate that SEA and SWAP induce PBMC proliferation through distinct intracellular signaling pathways. Moreover, the weaker response of PBMC to SEA compared to SWAP stimulation suggests down-regulation of cells from intestinal chronic schistosomiasis patients to SEA, which may occur during immunomodulation to S. mansoni response.
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PMID:Signal transduction events in human peripheral blood mononuclear cells stimulated by Schistosoma mansoni antigens. 1160 Feb 25


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