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 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.
 ...
PMID:Effect of cell division inhibitors on polyclonal activation can vary according to the target cell used. 39 5

We describe T560, a tissue culture-adapted B lymphoma derived from the gut-associated lymphoid tissue (GALT) of a (B10 x B10.H-2a H-4b)F1 hybrid mouse. This lymphoma is interesting and useful not only because it bears an unusual IgA receptor, fully described elsewhere, but also because it is potentially capable of presenting antigen to T cells restricted by the MHC of either parent. Here we document that T560 cells are IgG2a kappa +, Ia+, B220+, J11d.2+, CD3-, CD4-, CD5-, Mac 1-, Mac 2-, non-specific esterase-. They bind bromelain-treated mouse RBC (BrMRBC) in a PC chloride-inhibitable manner but do not bind SRBC, ox RBC (ORBC) or TNP-ORBC. Two lines, T560.1 and T560.2, and several clones are available. T560.1 and its clones contain low numbers of IgA rosette-forming cells (RFC), intermediate numbers of IgG2a RFC and moderately high numbers of IgG2b RFC; T560.2 and its clones contain moderately high numbers of IgA RFC and low numbers of both IgG2a and IgG2b RFC. Both lines stimulate both B10 and B10.A cells in mixed lymphocyte reactions (MLR) and present keyhole limpet hemocyanin (KLH) to KLH-reactive T cells. T560.2 populations are, however, more efficient possibly because they have somewhat higher proportions of brightly fluorescent Ia+ cells and secrete larger quantities of lymphokine than T560.1 cells. They present PC-conjugated KLH (PC-KLH) approximately 20 times more efficiently than unconjugated KLH, suggesting that their PC binding receptors function in antigen uptake. They constitutively produce IL-1, IL-4 and IL-6, but not IL-2, IL-5 or TGF beta. Neither their IgA nor their IgG receptor expression is affected by IL-4 or by IFNs-alpha, -beta, or -gamma. In their ability to bind BrMRBC and secrete IL-4, they resemble the CH12 lymphoma but differ from it in that they are of F1 hybrid origin, are CD5-, bear IgG2a rather than IgM, do not bind sheep erythrocytes and have a receptor for IgA not present on CH12.
 ...
PMID:T560: an (H-2b x H-2a) F1 hybrid, phosphorylcholine (PC)-binding, murine B cell lymphoma that bears receptors for IgA and IgG, presents antigen and secretes IL-4. 153 83

A GALT-derived B lymphoma, T560, that bears IgAR is described. T560 is IgG2a kappa +, Ia+, B220+, J11d+, Thy-1-, CD3-, CD4-, CD5-, Mac 1-, Mac 2-, nonspecific esterase negative and binds bromelain-treated mouse RBC but not SRBC or ORBC. It presents antigen, secretes IL-1, IL-4 and IL-6 but not IL-2, IL-5 or TGF beta and appears to be related to the Lyt 1+(CD5) lineage of B cells though it lacks Lyt 1. T560 bears IgAR that, on the cell surface, are completely cross-inhibited by low concentrations of IgM and by high concentrations of IgG2a and IgG2b. They do not appear to represent a cell-surface form of galactosyl transferase. They are inducible by high concentrations of IgA, sensitive to trypsin and insensitive to neuraminidase. They are down-regulated by activation of PKC with PMA, but their recovery is not inhibited by cycloheximide, indicating that they are not degraded or shed. They may either lose their affinity for IgA or be internalized without degradation. Seventy percent of IgA receptor activity is lost when T560 is treated with PI-PLC; part of this loss of activity is due to activation of PKC and is inhibited by staurosporine, but approximately 30% of it is not protected by staurosporine indicating that some, or all, of the IgA receptor of T560 is connected to the cell membrane via a GPI linker. The T560 IgA receptor could be related to the poly-Ig or M cell receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sensitivity of receptors for IgA on T560, a murine B lymphoma, to phorbol myristate acetate and to phosphatidylinositol-specific phospholipase C. 165 5

Cells from 6 of 14 different Ly-1+ murine B cell lymphomas bound to synthetic liposomes encapsulating fluorescein. The liposomes were made from distearoyl phosphatidyl choline (DSPC), distearoyl phosphatidyl glycerol (DSPG), and cholesterol. In all cases, liposome binding was due to recognition of phosphatidyl choline by the surface IgM on the tumor cells. Liposome binding could be inhibited by DSPC but not by DSPG, and the number of liposomes bound per cell was directly related to the cell surface concentration of IgM. The IgM secreted by a hybridoma derived from one of the lymphomas, CH12, was shown to agglutinate liposomes, and was used in a solid-phase immunoassay to study inhibition of liposome binding by pure phospholipids; DSPC and sphingomyelin both inhibited, whereas DSPG did not. The Ig borne by the six lymphomas that bind phosphatidylcholine also bind to both SRBC and bromelain-treated mouse erythrocytes. The idiotypic of CH12 IgM is similar to that expressed by Ly-1+ normal splenic B cells of the same specificity. The significance of these data in relation to other commonly studied autoantigens, and to the restricted specificity of normal Ly-1+ B cells is discussed.
 ...
PMID:Phosphatidyl choline is recognized by a series of Ly-1+ murine B cell lymphomas specific for erythrocyte membranes. 241 66

Antibodies specific for bromelain-treated mouse RBC (BrMRBC) are of interest as models of "natural autoantibodies" and because of their primary source is Ly-1+ (CD5+) B cells. In earlier work by others, anti-BrMRBC hybridomas prepared by using CBA or NZB "spontaneously activating" peritoneal B cells were all found to produce mAb with a single common H chain V region sequence, by using a novel gene (VH11p), and a single common L chain V region sequence, a member of the Vk9 group (VkBrMp). We prepared anti-BrMRBC hybridomas by using LPS-activated B10.A splenic B cells in order to reveal the maximum available diversity in this repertoire. Data based on binding studies, Northern blot analyses with V region-specific probes, and mRNA nucleotide sequence analysis indicated that there is combining-site diversity in the repertoire of anti-BrMRBC hybridomas. There was considerable variation in trimethylammonium (a constituent of phosphatidyl choline) binding efficiency, and one of the anti-BrMRBC mAb showed no detectable binding. Northern blot analyses indicated 6 of 11 mAb to be of the VH11p/VkBrMp type, including one dual reactive anti-[BrMRBC + SRBC] mAb. Sequence analyses of the H chain V regions of four of the non-VH11p mAb revealed utilization of four distinct VH, three of which are very similar to the VH expressed by Ly-1+ B cell clones or lymphomas, as reported by others. However, because the VH11p/VkBrMp-type mAb were all relatively efficient at lysing BrMRBC and binding trimethylammonium, we suggest that affinity considerations may determine the selective predominance of B cells with this V region configuration from an available repertoire of considerable diversity.
 ...
PMID:Diversity in the available repertoire of murine antibodies reactive with bromelain-treated isologous erythrocytes. 251 47

SJL mice are shown to be defective in their ability to develop suppressor cells following stimulation with Con A, a polyclonal T-cell activator. They make a normal proliferative response to this mitogen. In addition to this suppressor T-cell defect, the SJL mouse (unlike most mouse strains) does not develop a spontaneous antibody response to bromelain-treated autologous red blood cells (BrMRBC) in vitro. Although the SJL makes a normal proliferative response to LPS, antibody-forming cells against bromelain-treated autologous red blood cells are not increased following LPS in vivo nor does it manifest an increased response to SRBC or TNP. This may signify the presence of a functional B-cell defect in these animals. DBA mice are also shown, in this report, to have small numbers of antibody-forming cells to bromelain-treated autologous red blood cells but to be capable of responding to LPS in vivo with an increase in SRBC and TNP antibody responses.
 ...
PMID:Immunological defects in SJL mice. 294 46

The increase in autoantibodies with age of both experimental animals and humans has been thought to reflect a shift in the antibody repertoire from foreign to self antigens. In mice, before immunization, the age-associated increase in antibodies reactive with a prototypic autoantigen, bromelain-treated autologous erythrocytes (BrMRBC), reflected a 3-fold increase in serum IgM and the number of IgM-secreting spleen cells in old compared with young mice. However, the percentage of the IgM-secreting spleen cell repertoire reactive with BrMRBC in old mice was actually approximately 50% that in young mice. In contrast, after immunization with sheep erythrocytes (SRBC), old mice showed a 5-fold increase in the percentage of IgM-secreting cells reactive with BrMRBC while young mice showed no significant increase. The converse is true for the percentage of IgM-secreting spleen cells in old mice specific for SBRC, which is 10% the number generated by young mice. The increased autoantibody response of old mice is not, however, linked to their poor response to the nominal antigen. Thus, immunization with phosphorylcholine (PC) conjugated keyhole limpet hemocyanin, an antigen that induces a comparable anti-PC response in old and young mice, also induced more autoantibody forming cells in old than young mice. The increased autoantibody response of old mice after immunization can be accounted for by both an increased number of Ig-secreting spleen cells as well as an increased percentage of the expressed repertoire of IgM-secreting spleen cells that react with autoantigens.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dysregulation of the humoral immune response in old mice. 757 1

Aged humans and experimental animals are impaired in their responses to most foreign antigens although they produce greater amounts of autoantibodies. We have examined the effect of age on the production of antibodies to a prototypic foreign antigen, sheep erythrocytes (SRBC), and to a prototypic autoantigen, bromelain-treated mouse erythrocytes (BrMRBC), in young and old mice before and after immunization with SRBC. Old mice express more anti-BrMRBC plaque-forming cell (PFC) antibodies before and an even greater number after immunization with SRBC than young mice. Conversely, old mice produce far fewer anti-SRBC PFC than young mice following immunization with SRBC. We hypothesized that the differences in the responses of old mice to BrMRBC and SRBC reflects differences in the activity of CD5+ and CD5- B cells. To test this hypothesis we immunized young and old mice with foreign antigens reported (and confirmed in our studies) to stimulate CD5+ B cells [TNP-ficoll and phosphorylcholine-keyhole limpet hemocyanin (KLH)] or CD5- B cells (SRBC and TNP-KLH). We found that the PFC response of old mice to antigens mediated by CD5+ B cells was equal to or greater than that of young mice. In contrast the PFC response of old mice induced by antigens mediated by CD5- B cells was only 10% that of young mice. Thus it appears that the immune response of old mice is well maintained for antigens which elicit a CD5+ B cell response but not for those which elicit a CD5- B cell response.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of age on the expressed B cell repertoire: role of B cell subsets. 769 39