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)

Treatment of mouse erythrocytes with the proteolytic enzymes, bromelain, reveals antigenic determinants not normally exposed on the erythrocyte surface. It was found that not only NZB mice, a known autoimmune strain, but also several normal strains of mice contain cells in small numbers in their spleens and in larger numbers in their peritoneal cavities which will form plaques against bromelain-treated MRBC. During in vitro culture the number of anti-BR-MRBC PFC increases slightly in the spleen cell populations whereas the number of these PFC in peritoneal cells increases dramatically to as many as 100,000 PFC/10(6) cells. The plaques detected in this assay contain a central lymphoid cell and their development, which requires the presence of complement and protein synthesis, is inhibited by anti-mouse immunoglobulin.
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PMID:The properties of plaque-forming cells from autoimmune and normal strains of mice with specificity for autologous erythrocyte antigens. 5 84

The activity of Nocardia water-soluble mitogen (NWSM) and LPS were compared in several experimental systems, since both compounds are B-cell mitogens and polyclonal activators in vitro. The results reported here demonstrated that NWSM like LPS also has a strong adjuvant activity in vivo if administered in saline with a strong antigen (heterologous red blood cells) or even with a weak immunogen such as theta alloantigen. However, in contrast to LPS, NWSM administered to mice failed to induce in vivo proliferation of lymphocytes, polyclonal activation and PFC against syngeneic bromelain-treated erythrocytes and thymocytes. It is possible therefore, that different mechanisms may be responsible for adjuvant activity of NWSM and LPS.
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PMID:Nocardia water-soluble mitogen and lipopolysaccharide. Comparative study of two adjuvants and B-cell mitogens in mice. 32 90

When normal mouse spleen cells are cultured in vitro, large numbers of cells develop that produce antibody toward antigens found on bromelain-treated mouse erythrocytes (BrMRBC). The in vitro culture also generates T cells that mediate DTH toward these antigens. We have suggested that under in vivo conditions, suppressor T cells maintain these immune responses at a low level but that this suppression wanes when the cells are cultured in vitro. The present study examines the effect of concanavalin A (Con A) on the in vitro development of humoral and cell-mediated immunity to Br-MRBC. Mitogenic concentrations of Con A prevented the development of both the PFC and TDTH responses toward BrMRBC. The Con A-induced suppression was due to the induction of suppressor T cells; thus the addition of Con A-activated cells to fresh spleen cell cultures prevented the development of both the PFC and TDTH response against BrMRBC.
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PMID:The in vitro suppression of spontaneous erythrocyte autoimmune responses with lymphocytes activated with concanavalin A. 36 37

The effects of inhibitors of cell division on polyclonal stimulation induced either by bacterial lipopolysaccharide (LPS) or by a synthetic adjuvant, MDP, were compared, using different target cells. Doses of colchicine that prevented 3H-thymidine incorporation also prevented the induction of antibodies against TNP and against an altered self antigen: bromelain-treated mouse red blood cells (br-MRBC). Under identical conditions, incubation with cytosine arabinoside (CA) strongly prevented the induction of anti-TNP PFC and to a lesser degree anti-SRBC PFC. However, the number of anti br-MRBC PFC was unchanged even when a dose of CA which inhibits totally the incorporation of 3H-thymidine was used. Our findings indicate that the general term "polyclonal stimulation" may concern at least two different types of cell populations and therefore we strongly stress the importance of choosing similar targets in comparative experiments.
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PMID:Effect of cell division inhibitors on polyclonal activation can vary according to the target cell used. 39 5

Peritoneal cell cultures from NZB and C57BL/6 mice develop large numbers of PFC directed against antigens present on bromelain-treated isologous erythrocytes. The development of these autoimmune PFC can be suppressed by the addition of small numbers of BrMRBC at the start of the culture period. The possibility that the development of the plaque is prevented by the presence of antigen in vivo is discussed.
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PMID:Antigen suppression of the in vitro development of plaque-forming cells to autologous erythrocyte antigens. 110 5

RIIIS/J mice produce low antibody responses to several polysaccharide Ag of bacterial origin. They have low levels of serum IgM and IgG3 and high levels of serum IgG2a and IgG2b. Low serum IgM and IgG3 have been attributed to a low frequency of CD5 (Ly-1) B cells, which play an important role in the production of natural antibodies. Indeed, RIIIS/J mice have a low frequency of CD5 (Ly-1)+, IgM bright+, Ly-5 (B220)dull+ (i.e., CD5 (Ly-1) B) cells in their peritoneum. RIIIS/J mice treated with LPS produce a low anti-bromelain-treated mouse RBC splenic plaque-forming cell response and a normal anti-mouse transferrin splenic PFC response. Those data are compatible with the fact that CD5 (Ly-1) B cells contain the precursors of B lymphocytes secreting anti-bromelain-treated mouse RBC antibody. However, they have a higher frequency of IgM bright+, Mac-1+ cells in their peritoneum. These cells represent the CD5 (Ly-1) "sister population" of CD5 (Ly-1) B cells described by others. This suggests that characteristics usually associated with the CD5 (Ly-1) lineage are applicable only to the CD5 (Ly-1)+ Mac-1+ IgM+ population, but not the related CD5 (Ly-1)- Mac-1+ IgM+ population. RIIIS/J mice should thus prove a valuable model to study the CD5 (Ly-1) B cell lineage.
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PMID:Characterization of the immunodeficiency of RIIS/J [corrected] mice. I. Association with the CD5 (LY-1) [corrected] B cell lineage. 264 74

In lymphoid tissues of mice, there exist LPS-reactive B cells which can differentiate to IgM-secreting plaque-forming cells (IgM-PFC) and PFC secreting antibodies against bromelain-treated mouse erythrocytes (BrMRBC) by LPS activation. In this study, four groups of LPS-reactive B cells in spleen, peritoneal cavity and mesenteric lymph nodes from 2- and 10-week-old mice were compared and enumerated as precursors of IgM-PFC and anti-BrMRBC PFC on days 1 and 2 after LPS activation in quantitative culture conditions. The induction of each of four PFC responses in peritoneal cells was sensitive to LPS and anti-mouse IgM antibodies as much as the induction of the respective PFC response in spleen cells. The ratios of four groups of PFC to each other were different among three tissues and between two ages. These findings support the view that the four groups of LPS-reactive B cells in each tissue are mostly in distinct subpopulations of B cells from each other, and the respective groups of different lymphoid tissues at different ages belong to the same subpopulation.
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PMID:Ontogenetic development of lipopolysaccharide-reactive B cells against bromelain-treated mouse erythrocytes in mouse lymphoid tissues. 351 47

We demonstrated previously that B151K12 T cell hybridoma produces two distinct B cell differentiation factors, B151-TRF1 and B151-TRF2, capable of inducing differentiation of antigen-activated and unstimulated B cells into antibody-forming cells, respectively. In the present study we investigated the pathophysiologic relation of these factors with factors obtained from MRL/MP-lpr/lpr(MRL/lpr) mice and (C57BL/6 X DBA/2)F1 (BDF1) mice undergoing chronic graft-vs-host reaction (GVHR), representing a murine model of systemic lupus erythematosus with polyclonal B cell activation associated with the T cell hyperfunction. The functional and biochemical analyses revealed that B151-TRF2-like, but not B151-TRF1-like, activity was found in culture fluid supernatant (CFS) of lymphoid cells from MRL/lpr mice with lymphoproliferative syndrome. On the other hand, both B151-TRF1- and B151-TRF2-like activities were detected in CFS prepared from spleen cells of BDF1 mice undergoing chronic GVHR by the inoculation of parental DBA/2 spleen cells. Interestingly, spleen cells of BDF1 mice transferred with DBA/2 thymocytes preferentially elaborated B151-TRF1-like factor. Because BDF1 mice transferred with DBA/2 spleen cells but not with DBA/2 thymocytes developed a SLE-like syndrome exemplified by the appearance of Coombs' antibody and proteinuria, it seemed likely that production of B151-TRF2-like factor was closely associated with the onset of autoimmune disease. In fact, B151-CFS containing B151-TRF2 but not B151-TRF1 activity could induce a striking autoantibody production both in vivo and in vitro as detected by PFC responses of normal mice to bromelain-treated mouse red blood cells (BrMRBC). Moreover, it was demonstrated that in vitro anti-BrMRBC PFC responses induced by semipurified B151-TRF2 was markedly inhibited by addition of relevant anti-Ia antibody to the culture. Thus, the present study demonstrates that B151-TRF2 represents one of the B cell differentiation factors responsible for polyclonal B cell activation leading to autoantibody production.
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PMID:Polyclonal B cell activation by a B cell differentiation factor, B151-TRF2. III. B151-TRF2 as a B cell differentiation factor closely associated with autoimmune disease. 354 18

Lipopolysaccharide (LPS)-induced plaque-forming cells secreting IgM (IgM-PFC) and antibodies against bromelain-treated mouse erythrocytes (anti-BrMRBC PFC) on Days 1 and 2 of cultures were quantitatively estimated in spleen cells from mice of various ages. The concentrations of the four groups of PFC changed independently with age. The LPS dose dependency of the PFC response was markedly different between PFC on Days 1 and 2, but not different between anti-BrMRBC PFC and IgM-PFC or between 2- and 10-week-old mice. In a second experiment, spleen cells from 2- and 10-week-old mice were separated into subpopulations with or without Fc receptors, C3 receptors, or Ia antigens, and the LPS-induced PFC responses were quantitatively assessed in each subpopulation. Both the receptor-bearing and -lacking populations included LPS-reactive B cells, and the percentages of the LPS-reactive B cells recovered in the receptor-bearing population increased with age. However, the percentages of anti-BrMRBC PFC recovered in each receptor-bearing or -lacking population were different from those of IgM-PFC. In Ia- populations, the percentages of IgM-PFC on Day 2 were obviously higher than those on Day 1, and both of the percentages increased with age. These results suggest that the four groups of LPS-reactive B cells can be discriminated from each other by their LPS dose dependency and their cell surface markers, and that they develop differently during ontogeny.
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PMID:Ontogenical studies on kinetics of lipopolysaccharide-induced response to bromelain-treated mouse erythrocytes in mouse spleen cells. II. Response of spleen cells with or without Fc receptors, C3 receptors, or Ia antigens. 387 8

Normal mice have large numbers of cells (PFC) making antibody to an autoantigen which is exposed when their own erythrocytes are treated with proteolytic enzymes. Antibody against this antigen can be demonstrated in serum by haemolysis tests against the treated cells; this antibody rises to high levels within 2 to 3 days after injection of E. coli lipopolysaccharide. using quantitative absorption tests we have located the 'bromelain mouse' (BrM) autoantigen in the gastrointestinal tract as well as in erythrocytes; this distribution pattern resembles that of classical blood group antigens. We have described the ontogenetic development of PFC, B cells capable of activation by LPS, serum antibody and antigen. Free antigen is found in the gut shortly after birth. B cells rise rapidly to high levels in the peritoneal cavity, but require a short period of culture to release detectable antibody. PFC and B cells increase more slowly in spleen to adult levels by 3 weeks of age. The serum antibody lags behind PFC development. The pattern is consistent with an early stimulation of B cells in the peritoneal cavity by gut-derived antigen. We discuss the possible relationship of this autoimmune response to high natural responses against other autoantigens in mice, man and other species.
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PMID:Ontogeny of the autoimmune reaction in normal mice to antigens in erythrocytes and gut. 702 Oct 25


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