Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The administration of low-density lipoproteins from chicken egg yolk (EyLDL) to mice induced T-dependent antibodies against bromelain-treated mouse erythrocytes (BrMRBC). The anti-BrMRBC antibodies produced antigen specifically by EyLDL appear to be identical to the antibodies produced polyclonally by lipopolysaccharide (LPS); both antibodies reacted with the liposomes of phosphatidylcholine and showed identical idiotypic patterns. It is suggested that the anti-BrMRBC antibodies may be produced antigen specifically by exogenous antigens to be useful to the mouse. The activation of anti-BrMRBC B cells specifically by EyLDL or polyclonally by LPS resulted in neither expansion nor regression of anti-BrMRBC LPS-reactive B cells. This finding indicates that the population size of anti-BrMRBC LPS-reactive B cells is controlled independently by exogenous specific or polyclonal stimuli.
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PMID:Induction of antibody response to bromelain-treated mouse erythrocytes by low-density lipoproteins from chicken egg yolk. 245 50

The ratio of lipopolysaccharide (LPS)-reactive B cells specific for bromelain-treated mouse erythrocytes (BrMRBC) to general LPS-reactive B cells is far higher in the peritoneal cavity of normal mice than in their spleen. To investigate the high concentration of anti-BrMRBC LPS-reactive B cells in the peritoneal cavity, spleen and peritoneal cells from (CBA/N X C3H/He)F1 female normal mice were injected intravenously and intraperitoneally into F1 male X-linked immunodeficient mice. Both groups of B cells in the intravenously transferred cell population were able equally to home in the spleen, but only anti-BrMRBC LPS-reactive B cells could be detected migrating into the peritoneal cavity. About half the anti-BrMRBC LPS-reactive B cells in the intraperitoneally transferred cell population could be recovered from the peritoneal cavity, but general LPS-reactive B cells were eliminated rather rapidly from the peritoneal cavity. Neither group of B cells could be detected migrating from the peritoneal cavity into the spleen. These findings suggest that the high concentration of anti-BrMRBC LPS-reactive B cells in the peritoneal cavity may be caused by their preferential ability to penetrate into the peritoneal cavity through circulation and survive there.
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PMID:Lipopolysaccharide-reactive B cells against bromelain-treated mouse erythrocytes: preferential migration to and survival in the peritoneal cavity. 278 44

The aim was to develop a cellular-ELISA assay to detect natural autoantibodies specific for bromelain-treated mouse red blood cells (BrMRBC). High, unexpected IgM titres against normal mouse red blood cells (NMRBC) were detected in day 7-14 sera of CBA mice treated with E. coli lipopolysaccharide (LPS). These "autoantibodies" bound to normal mouse red blood cells in the presence or absence of commonly used c-ELISA adhering agents. Such high reactivity to NMRBC was never detected using complement dependent haemolytic assays in earlier work in this system. The question whether these IgM alpha-NMRBC molecules were binding nonspecifically (via Fc) or specifically (via Fab) was answered indirectly by comparing the binding titres of LPS-stimulated serum and several purified IgM antibody preparations (alpha-PC, alpha-KLH, MOPC 104E) on the same antigen coated plates. The observed binding ratios (titre on antigen X: titre on NMRBC) varied widely between different antibody sources, indicative of specific binding. In addition no significant unequivocal binding against NMRBC could be detected in vivo (LPS-stimulated mice) nor could bound IgM antibody be detected in a suspension-c-ELISA assay (high binding titres to BrMRBC could be detected in the latter test system). In conventional c-ELISA assays, modification of normal erythrocyte by adhesion to plastic microtitre plates appears to expose or create "neoantigens" on NMRBC which are not encountered in suspension-type c-ELISA, nor in lytic or agglutination assays where the erythrocyte targets are in suspension at physiological pH and isotonicity.
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PMID:IgM anti-erythrocyte autoantibodies specific for buried and neo-antigens using cellular-ELISA assays. 317 55

A preliminary experiment showed that the supernatants of in vitro cultured peritoneal cells (rich in Ly-1 B cell subset shown to secrete most IgM autoantibodies against bromelain-treated mouse red blood cells (BrMRBC) and DNA) from different mouse strains did not contain any significant antibody activity against DNA and cytoskeleton proteins, although the presence of anti-BrMRBC antibodies was clearly evident. Therefore, we investigated comparative natural antibody (NAb) specificities against an antigen panel (DNA, cytoskeleton proteins, IgG, bovine serum albumin (BSA), BrMRBC, trinitrophenyl (TNP), and trimethylammonium (TMA) haptens) among Ig-secreting hybridoma collections from the splenic (158) and peritoneal (230) immune compartments of autoimmune New Zealand black (NZB) and lipopolysaccharide (LPS)-stimulated BALB/c mice. The data showed: (i) isotypic restriction (mu and gamma 3 only), predominance of TMA ion-reactive (including BrMRBC) but negligible anti-DNA-reactive antibody specificities, and lack of simultaneous polyspecific widespread reactivity (i.e. at least four or more antigens) against DNA and cytoskeleton proteins in the peritoneal cavity; (ii) predominance of simultaneous widespread polyspecific reactivity against DNA and cytoskeleton proteins but negligible or no TMA hapten-reactive antibody specificities in the spleen. These observations reflect certain differences in the B cell repertoire of peritoneal cavity (rich in Ly-1 B cells) compared with spleen. The NAb against BrMRBC and those reactive with DNA and cytoskeleton proteins, which have been suggested to be secreted by the Ly-1 B cell subset, are distinguishable on the basis of the presence of separate recurrent idiotypes and preferential localization of B lymphocytes directed against these autoantigens.
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PMID:Comparative analysis of natural antibody specificities among hybridomas originating from spleen and peritoneal cavity of adult NZB and BALB/c mice. 325 8

A high frequency of clonal precursor B cells producing lytic antibodies to syngeneic erythrocytes treated with bromelain (BMRC) is revealed in normal mouse spleen cells by lipopolysaccharide-driven limiting dilution analysis. All such specificities are recovered as activated blasts after density gradient fractionation, the "small lymphocyte" pool being depleted of anti-BMRC reactivities. In contrast, the spleens of athymic (nude) mice contain undetectably low frequencies of these specificities in either lymphocyte compartment. Transfer of relatively low numbers of normal syngeneic splenic T lymphocytes to adult nude mice restores the high frequency of anti-BMRC clonal precursor B cells, again in the activated, but not in the resting spleen cell fractions. Large total T cells are more than tenfold better than resting T cells in reconstitution potential, as are enriched CD4+ as compared to CD8+ cells which are practically devoid of activity in this respect. These results apply exclusively to B cells at a differentiative stage that allows for extensive clonal expansion, since there is a marked difference between the frequency of clonal precursors determined by limiting dilution analysis and the frequency of Ig-secreting plaque-forming cells of the same specificity, and induced by the same mitogen in short-term cultures. The implications of these findings for the physiology of autoreactivity and repertoire selection in the compartment of perinatal B cells are discussed.
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PMID:T cell dependence of the "natural" autoreactive B cell activation in the spleen of normal mice. 326 23

The murine response to bromelain-treated mouse red blood cells (BrMRBC) is derived from Ly-1 B cells. It has been proposed that this B-cell subset produces a variety of other autoantibodies and is elevated in autoimmune mouse strains. We have studied the ability of MRL lpr/lpr and the non-autoimmune congenic MRL +/+ mice to make autoantibodies to BrMRBC and immunoglobulin (rheumatoid factors, RF). Following lipopolysaccharide (LPS) stimulation we found the numbers of autologous plaque-forming cells (PFC) to be low in both lpr and MRL +/+ mice, suggesting low Ly-1 B-cell numbers. This observation is consistent with the view that Ly-1 B cells in the mouse may not give rise to pathologically relevant RF.
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PMID:The relationship between induced and spontaneous autoantibodies in MRL mice: the role of Ly-1 B cells? 329 11

Auto-antibody responses and circulating immune complex levels of mice with abnormal reactions to endotoxin were investigated after injection with the bacterial product. It was observed that C3H/HeJ mice displayed very high background plaque-forming cell responses towards bromelain-treated isologous erythrocytes which were slightly enhanced by endotoxin treatment. The same animals, however, did not bear autohaemolysins in their serum, but became so upon endotoxin injection. A possible relationship between the high background reactivity of C3H/HeJ mice and the low toxicity of endotoxin in these animals is discussed. Neither untreated nor lipopolysaccharide-injected C3H/HeJ mice showed significant immune complex levels in their sera. This may be explained by their hyporesponsiveness, but by a low sensitivity to the toxic effects of endotoxin as well. C5-deficient and C5-sufficient mice showed similar auto-immune reactions, indicating that C5a, which is responsible for other effects of endotoxin, is not involved in endotoxin-induced auto-immunity.
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PMID:Endotoxin-induced auto-immunity in mice. II. Reactivity of LPS-hyporesponsive and C5-deficient animals. 341 May 56

The effect of cyclosporine (CsA) on the CH12 murine B cell lymphoma was investigated to determine whether sensitivity to this agent is retained by malignant B cells. This tumour produces an antibody to bromelain-treated red blood cells and may represent transformation of a B cell with certain activation properties associated with early resting B cells. In in vitro cultures, the growth and proliferation of CH12 were inhibited by CsA in concentrations of 0.1-1.0 microgram/ml; these levels were ineffective against non-lymphoid tumours, although some non-specific cell toxicity was noted at higher levels. IgM antibody production, as measured by enzyme-linked immunosorbent assay (ELISA), was inhibited over the same range. CH12 cells stimulated by lipopolysaccharide, however, were less sensitive to CsA than untreated cells. These studies indicate that malignant B cells may be sensitive to CsA, perhaps reflecting their derivation from a functionally distinct B cell population with enhanced drug sensitivity.
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PMID:Cyclosporine inhibition of a murine B cell lymphoma. 348 33

Sera from mice injected 4 days earlier with lipopolysaccharide lysed mouse RBC treated with bromelain (brom). This lytic activity was totally inhibited by including phosphatidylcholine at final concentrations of about 2 micrograms/ml, or more, in the lytic mixtures. In contrast, the lytic activity of antibodies against rat RBC was not inhibited, even at concentrations of phosphatidylcholine up to 2.5 mg/ml. Various components of the phosphatidylcholine molecule, and other lipids including the closely-related molecule dipalmitoyl phosphatidyl-dimethyl-ethanolamine which is identical to dipalmitoyl phosphatidylcholine, except for the absence of a CH2 group on the polar head group, did not inhibit lysis by the autoantibodies. Autoantibodies against mouse brom RBC, but not antibodies against rat RBC, bound to, and could be eluted from, phosphatidylcholine molecules attached to an insoluble matrix. Liposomes of phosphatidylcholine prepared in the presence of phosphatidic acid or phosphatidylinositol did not inhibit the lysis of mouse brom RBC by autoantibodies to the same extent as liposomes of only phosphatidylcholine. This suggests that phosphatidylcholine is recognized by the autoantibodies only if presented in a certain configuration. We suggest that the function of these autoantibodies may be to facilitate the removal of membrane-damaged cells from the body. Such cells may arise by the process of ageing, or because of the effects of infectious agents such as viruses.
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PMID:Autoantibodies against mouse bromelain-modified RBC are specifically inhibited by a common membrane phospholipid, phosphatidylcholine. 400 27

In a serum free, 2-mercaptoethanol supplemented culture medium muramyl dipeptide (MDP) is able to increase the number of plaque-forming cells (PFC) directed against syngeneic, bromelain-treated red blood cells (br-MRBC) and against an autoantigen, mouse albumin. The non-specific stimulation of anti-br-MRBC PFC by MDP, as by bacterial lipopolysaccharide (LPS), can be observed in spleen cell populations depleted of adherent and phagocytic cells, and in nu/nu spleen cell cultures. However, the kinetics of the induction of anti-br-MRBC PFC in murine spleen cell cultures in presence of LPS or of MDP are not identical. Moreover, MDP is able to stimulate C3H/He Orl (LPS low-responder strain) cells. Thus, the mechanisms of non-specific stimulation by MDP or by LPS could be different. Experiments done with thirteen structural analogues of MDP showed that there exists a good correlation between the adjuvant activity and the ability to induce anti-br-MRBC PFC.
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PMID:Induction of antibodies directed against self and altered-self determinants by a synthetic adjuvant, muramyl dipeptide and some of its derivatives. 616 92


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