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

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymectomy of BALB/c mice on day 3 of life results in the development of autoimmune gastritis (AIG) due to the absence of CD4(+)CD25(+) regulatory T cells. However, depletion of CD4(+)CD25(+) T cells by treatment with anti-CD25 rarely resulted in AIG. Depletion was efficient, as transfer of splenocytes from depleted mice induced AIG in nu/nu mice. One explanation for this result is that CD4(+)CD25(-) T cells upon transfer to nude recipients undergo lymphopenia-induced proliferation, providing a signal for T cell activation. Cotransfer of CD25(+) T cells did not inhibit initial proliferation but did suppress AIG. Surprisingly, immunization with the AIG target Ag, H/K ATPase, in IFA failed to induce disease in normal animals but induced severe AIG in CD25-depleted mice. These results demonstrate that second signals (nonspecific proliferation, TCR activation, or inflammation) are needed for induction of autoimmunity in the absence of CD25(+) regulatory T cells.
...
PMID:Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. 1205 2

A CD4(+) T cell response to the gastric H/K ATPase beta-subunit (H/Kbeta) is required for the onset of experimental autoimmune gastritis in BALB/c mice. The extent to which endogenous H/Kbeta contributes toward the tolerance of the H/Kbeta-specific T cell repertoire in normal individuals is not known. By comparison of T cell responses in H/Kbeta-deficient (o/o) and H/Kbeta-expressing BALB/c mice, in this work we show that the endogenous H/Kbeta autoantigen plays a major role in the tolerance of pathogenic H/Kbeta-specific T cells. First, T cell-dependent Ab responses to the H/Kbeta Ag were enhanced in H/K ATPase-immunized H/Kbeta-deficient mice compared with wild-type mice. Second, peptide immunization experiments indicated that immune responses to the major gastritogenic epitope of the H/K ATPase, namely H/Kbeta(253-277), were significantly more vigorous in H/Kbeta-deficient mice compared with wild-type mice. Third, unfractionated splenocytes from H/Kbeta-deficient mice, but not H/Kbeta-expressing mice, induced autoimmune gastritis after adoptive transfer to BALB/c nude mice. The enhanced responses to H/Kbeta in H/Kbeta-deficient mice were shown to be intrinsic to CD4(+)CD25(-) T cells rather than a change in status of CD4(+)CD25(+) regulatory T cells. We conclude from these studies that the H/Kbeta-specific T cells in wild-type mice represent the residue of a T cell repertoire, directed toward a single determinant, that has been subjected to partial tolerance induction.
...
PMID:Endogenous H/K ATPase beta-subunit promotes T cell tolerance to the immunodominant gastritogenic determinant. 1219 2

Human autoimmune gastritis (AIG) is an organ-specific inflammatory disorder leading to gastric atrophy and pernicious anemia. Gastric H+,K(+)-ATPase was identified as the autoantigen in both human disease and experimental murine AIG (EAIG). Studies of EAIG significantly contributed to current knowledge of human AIG, but to what extent EAIG mimics AIG is still debated, and the autoantigenic epitopes in AIG are yet unknown. This study aimed to identify the H+,K(+)-ATPase epitopes recognized by gastric T cell clones from AIG patients, to define their TCR Vbeta usage and epitope-induced cytokine response. Sixteen H+,K(+)-ATPase-reactive CD4+ gastric T cell clones of four AIG patients were tested for proliferation to overlapping 15-mer peptides spanning the a and beta chains of H+,K(+)-ATPase. We identified 6 epitopes in the a chain and 5 in the beta chain; TCR Vbeta usage was not restricted. Four (36%) of the 11 H+,K(+)-ATPase epitopes recognized in AIG were found to overlap with epitopes that are relevant in EAIG, including a previously described gastritogenic epitope. Gastric T cell recognition of the peptide epitopes resulted in secretion of Th1 cytokines. Our data suggest a striking similarity between human AIG and EAIG, at the epitope level, with regard to cytokine secretion and likely also with regard to pathogenic mechanisms.
...
PMID:Characterization of H+,K+-ATPase T cell epitopes in human autoimmune gastritis. 1264 53

CD3 antigen, formerly thought to be specific for T lymphocytes, has been found on gastric parietal cells in animals and humans. The common anti-CD3 antibodies recognize the epsilon subunit, which has a role in signal transduction. The aim of this study was to immunostain stomach specimens from humans and different animal species for CD3 antigen to determine if CD3 antigen is conserved across species and if CD3 antigen expression is altered in humans by use of certain drugs or the presence of gastritis. Gastric biopsies from 50 humans and necropsy sections from 13 different animals were immunostained using commercial anti CD3 epsilon antibodies on an automated immunostainer. Sections of stomach from four mice lacking the gastric H+,K(+)-ATPase alpha-subunit and four control mice were similarly immunostained. CD3 epsilon antigen expression in cytoplasm and cell membranes of gastric parietal cells was graded subjectively based on the number of positive cells. CD3 epsilon antigen was found on gastric parietal cells in all but one species studied, with varying expression in membranes and cytoplasm. There was a trend toward a decreased frequency of CD3+ cells in biopsies from patients on drugs (n = 23) compared to those on no drugs (n = 27). This trend was most marked in patients on H2 receptor antagonists. There was no correlation between CD3 expression and inflammation or Helicobacter pylori (H. pylori) infection. There was loss of CD3 expression in parietal cells in mice lacking the alpha-subunit of H+,K(+)-ATPase. These findings support previous observations that CD3 antigen is present in gastric parietal cells, and suggest that it may function in signal transduction during acid secretion.
...
PMID:Expression of CD3 epsilon subunit in gastric parietal cells: a possible role in signal transduction? 1281 14

Over the past 10 years experimental autoimmune gastritis has been established as a highly defined model of organ-specific autoimmunity. Autoimmune gastritis represents one of the few autoimmune diseases in which the causative autoantigens, namely the gastric H/K ATPase alpha- and beta-subunits, are defined. Furthermore, it has been clearly established that a CD4+ T cell response to the H/K ATPase beta-subunit, in particular, is essential for the initiation of autoimmune gastritis. The immunopathology of autoimmune gastritis is due to a disruption of the normal developmental pathways of the mucosa, rather than a direct depletion of the end-stage parietal and zymogenic cells. CD4+CD25+ regulatory T cells were first described in experimental autoimmune gastritis and there has been a recent explosion of interest in the potential role of these immunoregulatory T cells in protection against a variety of autoimmune diseases. The availability of H/K ATPase deficient mice has begun to provide considerable insight into the basis for tolerance to the gastric autoantigens. Experimental autoimmune gastritis has also provided valuable insight into our understanding of the genetics of disease susceptibility and four distinct genetic regions have been identified which confer susceptibility to this organ-specific disease. The highlights of these recent advances are the subject of this review.
...
PMID:Immunopathogenesis, loss of T cell tolerance and genetics of autoimmune gastritis. 1284 83

54 children at the age of 3-15 suffering from HP-associated CG were examined. Antibodies to H+/K(+)-ATPase of gastric parietal cells were determined with the help of the immune-enzyme analysis method. It was discovered that antibodies to H+/K(+)-ATPase are found in 27.7% of children. Concomitant autoimmune diseases, pangastritis, morphologic symptoms of the pre-atrophic stage of autoimmune gastritis as well as the drop of secretion at the fasting phase were discovered more often in antibody-positive patients. The successful eradication of HP in two children resulted in the disappearance of anti-parietal autoantibodies.
...
PMID:[Antibodies to H+/K+-ATPase of gastric parietal cells in children with Helicobacter pylori associated chronic gastritis]. 1455 39

Neonatal thymectomy (NTx) in mice induces a group of alterations in the immune system homeostasis that results in the development of a variety of organ-specific autoimmune diseases such as gastritis, thyroiditis, oophoritis and orchitis. Given the importance of self-antigen expression in thymus for the control of autoreactive cells and generation of regulatory cells, we have compared the expression of parietal cell antigen in two strains of mice with the same H-2: BALB/c (susceptible to develop gastritis after NTx) and DBA/2 (resistant). We detected mRNA of HK-ATPase alpha and beta chains in day 1 thymi of both strains. Fifty percent of BALB/c mice presented mRNA levels similar to DBA/2. However, lower mRNA levels were found in the remaining BALB/c mice that may correspond to those that would develop AIG after NTx. Since the presence of the antigen in periphery is also necessary for the induction of regulatory cells, we have compared both strains observing in day 1 stomachs from resistant DBA/2 strain, a significantly higher content of positive cells for HK-ATPase subunits than stomachs from susceptible BALB/c strain. Also, the presence of antinuclear Abs in NTx BALB/c mice makes this model a useful experimental system for analyzing the responsible mechanisms breaking the non-specific self-tolerance.
...
PMID:HK-ATPase expression in the susceptible BALB/c and the resistant DBA/2 strains of mice to autoimmune gastritis. 1456 57

Experimental autoimmune gastritis (EAG) is a model of human autoimmune gastritis, the underlying cause of pernicious anaemia. It is characterised by gastric mononuclear cell infiltrates, destruction of parietal and zymogenic cells, and autoantibodies to parietal cell-associated H(+)/K(+) ATPase. Here, we have investigated the role of CCR5 in the development of EAG. We found that the development of EAG was not prevented in CCR5-deficient mice. Using reverse-transcriptase analysis of stomachs from normal and gastritic mice we found no difference in expression of CCR5 and its chemokine ligands MIP-1alpha, MIP-1beta, and RANTES. We also found that the CCR5 antagonist met-RANTES failed to prevent the development of EAG induced by neonatal thymectomy. These observations suggest that the CC chemokine receptor CCR5 is not essential for development of EAG.
...
PMID:Chemokine receptor CCR5 is not required for development of experimental autoimmune gastritis. 1459 23

We examined: 1 group--16 children with chronic gastritis (CG) and autoimmune thyroiditis (AT); 2 group--41 children with functional thyroidal pathologies; 3 group--23 children with CG only. The average age in all groups was 11.17 +/- 2.98. HP (68%) was revealed equally frequently in all the groups. Antibodies to H+/K(+)-ATPase of parietal cells were revealed in the first and second groups only (31-36%), p < 0.05 as compared to the third group. CG of the stomach body was more frequently revealed in the first group using endoscopic and histological tests. The second group had more frequent and more apparent lesions of the antral part. Thus, in case of concomitant diseases of the thyroid gland CG has an autoimmune nature of an inflammation of the mucous coat of the stomach.
...
PMID:[Chronic gastritis in children with concomitant diseases of the thyroid gland]. 1465 36

Experimental autoimmune gastritis (EAG) characterised by mononuclear cell infiltrate, parietal and zymogenic cell destruction and circulating autoantibodies to gastric H(+)/K(+)ATPase is an animal model for human autoimmune gastritis, that leads to pernicious anaemia. We have previously shown that Fas has a role in initiating damage to target cells in EAG. Here we used three strategies to examine the role of TNFalpha in this disease. We administered neutralising anti-TNFalpha antibody either as a single injection or as twice weekly injections for 8 weeks to mice subjected to neonatal thymectomy-induced EAG. To address the role of apoptotic signals through TNFR1, TNFR1 deficient mice were either neonatally thymectomised or crossed to PC-GMCSF transgenic mice that spontaneously develop EAG. Neonatally thymectomised mice treated with anti-TNFalpha antibody developed destructive gastritis and autoantibodies to gastric H(+)/K(+)ATPase similar to control mice. Following either neonatal thymectomy or crossing to PC-GMCSF transgenic mice, TNFR1 deficient mice developed autoantibody-positive destructive gastritis at similar frequency compared with wild type and heterozygous littermates. Our observations that neutralisation of TNFalpha and absence of TNFR1 has no discernible effect on development of EAG suggest that TNFalpha is not required for mucosal cell damage or development of autoimmune gastritis. While blocking TNFalpha activity has therapeutic benefit in certain autoimmune diseases, this is not the case for EAG.
...
PMID:Tumor necrosis factor alpha is not implicated in the genesis of experimental autoimmune gastritis. 1470 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---