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 ascites form of a chemically induced guinea pig hepatoma, line-10, was resistant to killing in vitro by xenogeneic antibody and guinea pig complement. Pretreatment of line-10 cells with certain proteolytic enzymes rendered tham susceptible to the killing action of antibody and guinea pig complement. The effects of enzyme pretreatment were dependent on enzyme concentration, temperature, and could be blocked by addition of competitive or non-competitive inhibitors. The effect of the enzyme treatment could reversed by incubating the treated cells at 37 degrees C (but not at 0 degrees C), in the absence of the enzyme. Effective enzymes included ficin, bromelain, pronase, elastase, papain, trypsin, collagenase, lipases type I and type VI, and the neuraminidase preparation isolated from Clostridium perfringens. The activity of the lipase preparations and the neuraminidase preparation isolated from Clostridium perfringens appeared to be caused by proteolytic enzyme contamination. Enzyme preparations that proved ineffecitve in rendering the line-10 cells sensitive to killing by antibody and guinea pig complement included DNase, RNase, beta-glucuronidase type 6A or type B10, hyaluronidase type V or type VI, and pectinesterase.
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PMID:Lysis of tumor cells by antibody and complement. VI. Enhanced killing of enzyme-pretreated tumor cells. 17 70

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.
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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

We have analyzed the combining site diversity of murine antibodies reactive with bromelain-treated mouse RBC (BrMRBC) in B10.A mice. Although several VH and V kappa genes are used to generate antibodies of this specificity, two combinations account for more than 80% of the repertoire from the spleen: VH11/V kappa 9 and VH12/V kappa 4. Antibodies representing these two predominant groups were found to correspond to two previously reported distinct cross-reactive Id families accounting for most of the anti-BrMRBC reactivity in several strains of mice. mAb of the VH11/V kappa 9 type bound the haptens trimethyl-ammonium and phosphorylcholine much more avidly (approximately 1000 fold) than did the VH12/V kappa 4 type antibodies. Both of these haptens represent constituents of phosphatidylcholine, which BrMRBC-specific antibodies are reported to bind. Despite this differential reactivity, members of both the VH11/V kappa 9 and VH12/V kappa 4 antibody groups lysed BrMRBC with similar efficiencies. These data suggest that the two major classes of BrMRBC-specific antibodies have at least partially different specificities and imply that the events that lead to their high frequencies in the CD5+ repertoire may result from different selective forces.
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PMID:Properties of murine antibodies from different V region families specific for bromelain-treated mouse erythrocytes. 199 63

5-15% of lymphocytes in the peritoneums of normal adult B10.H-2aH-4bp/Wts (2a4b) mice are CD5+ (Ly-1) B cells that recognize phosphatidyl choline (PtC), a phospholipid component of all mammalian cells. We produced a set of IgM-secreting hybridomas from the peritoneal cells of normal, adult 2a4b mice. We found that this set of hybridomas shows a similarly high frequency of antibodies specific for PtC (21 of 86) that also react with bromelain-treated mouse erythrocytes. Restriction fragment analysis of Ig gene rearrangements and analysis of expressed Ig idiotypes reveal that these cells use a restricted set of variable region genes to generate the PtC-specific antibodies. The Ig genes used by the PtC-specific hybridomas appear to be the same as those found in the PtC-specific Ly-1 B cell lymphomas, CH27 and CH34.
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PMID:Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline. 249 51

Most, if not all, autoantibodies specific for bromelain-treated mouse erythrocytes recognize the common membrane phospholipid, phosphatidyl choline (PtC). Anti-PtC antibodies are produced by 5%-15% of CD5+ Ly-1 B cells of normal unimmunized mice, but not by detectable numbers of conventional CD5- B cells. At 1 week of age PtC-specific B cells are undetectable but then increase dramatically over the next 3 to 4 weeks to reach adult numbers. We report here that PtC-specific Ly-1 B cells in B10.H-2aH-4bp/Wts mice predominantly express either of two heavy and kappa chain variable (V) region gene combinations. In addition, the sequence and length of DH genes are conserved among cells expressing the same V gene combination, and the V kappa-J kappa junctions of one group involve unusual splice sites. Preferential V gene rearrangement models are insufficient to explain the DH and V kappa-J kappa junctional sequences or the delayed appearance of this specificity, and so they cannot solely account for the high frequency of PtC-specific cells. These characteristics are more consistent with antigen selection. We therefore attribute the frequent use of the two V region gene combinations to selection for cells that express them and conclude that the expressed V gene repertoire of Ly-1 B cells in adult mice is influenced by antigen selection. Apparently, there is no selection for mutant anti-PtC antibodies of higher affinity during the formation of the Ly-1 B repertoire because the V region genes expressed by PtC-specific cells are unmutated. Our findings are consistent with an important, germ line-encoded function for the immunoglobulin products of these gene combinations.
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PMID:Biased immunoglobulin variable region gene expression by Ly-1 B cells due to clonal selection. 250 89

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.
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PMID:Diversity in the available repertoire of murine antibodies reactive with bromelain-treated isologous erythrocytes. 251 47

A series of 27 B-cell lymphomas (designated the CH series), induced in B10.H-2aH-4b p/Wts mice by intense adoptive immunization with sheep erythrocytes, was found to represent a subset of the total B-cell repertoire. This subset was characterized by expression of a limited number of Ig heavy chain variable regions, as evidenced by the presence of cross-reactive idiotypes and common antigen binding specificities. Twenty-one of the 27 CH lymphomas studied were classified into five groups, defined by a particular cross-reactive idiotype; four of these groups were linked in a single network. Seven of 16 idiotypes defined by absorption analysis were present on lymphomas bearing either kappa or lambda light chains and so were localized to the heavy chain variable region. The surface Ig on 14 CH lymphomas was found to be specific for epitopes on certain erythrocytes (bromelain-treated autologous erythrocytes, sheep, and chicken erythrocytes) or E. coli. We propose that the CH lymphomas represent the malignant counterparts of a subset of idiotypically related, normal B cells in B10.H-2aH-4b p/Wts mice. Perturbation of this idiotype network, by hyperimmunization with an antigen for which some of the members are specific (sheep erythrocytes), increases the risk for neoplasia. Possible mechanisms for this are discussed.
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PMID:Cross-reactive idiotypes and common antigen binding specificities expressed by a series of murine B-cell lymphomas: etiological implications. 258 25

The spleens of normal B10.H-2aH-4bp/Wts (2a4b) mice contain cells which, in response to mitogen stimulation, secrete hemolytic antibody specific for a determinant present on both sheep and bromelain-treated mouse erythrocytes. These cells were found to be Ly-1 positive. Approximately 50% of these cells bear surface immunoglobulin (sIg) with the same idiotype as the sIg of a 2a4b-derived B-cell lymphoma, CH12. Backcross analysis revealed H-2 control of the frequency of the idiotype-positive B cell. The regulatory gene did not correlate with the Igh-1 allotype, and analysis of 22 inbred mouse strains mapped the gene to the I-E subregion. Surprisingly, only strains homozygous for Ek alpha expressed the idiotype, and expression was a recessive trait. Possible mechanisms for this control of idiotype expression and its relation to lymphomagenesis are discussed.
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PMID:H-2 control of expression of an idiotype shared by normal B cells and a B-cell lymphoma. 392 82

We have previously described a murine B-cell lymphoma, CH12, the cells of which bear surface IgM reactive with sheep erythrocytes (SRbc) and which could differentiate to secrete hemolytic antibody. The question addressed in this paper was whether differentiation of CH12 cells could be influenced by interaction with regulatory T cells and antigen. If so, we wanted to know whether the conditions required differed from those known to govern similar interactions with normal B cells. We had two reasons for wanting to answer these questions. First, we wondered whether CH12 could be used as a clonal population of indicator cells to study the regulation of B cell differentiation and, second, we wanted to know the extent to which these neoplastic cells were still responsive to normal regulatory signals. The first addresses a major difficulty which must be faced in studies of normal B cell differentiation: to what extent is the interpretation limited by heterogeneity of the B cells used? The second relates to the nature of neoplasia and the possibility that neoplastic cells might be rendered harmless by inducing terminal differentiation. CH12 is one of a series of transplantable B cell lymphomas which arose in B10.H-2aH-4b p/Wts (2a4b) mice, following intense immunization with SRbc. It is a monoclonal tumor, all the cells of which bear membrane IgM(kappa) of a single idiotype, reactive with sheep and chicken Rbc and with bromelain-treated autologous mouse Rbc. The cells express KkAkEk and Dd antigens appropriate to the H-2a haplotype. During the latter stages of growth in vivo or in vitro, a small proportion (less than 3%) of the cells differentiate to secrete hemolytic antibody as measured by the Cunningham assay for plaque forming cells (PFC). We cultured CH12 cells for 3 or 4 days, together with antigen and spleen cells from primed animals, and assayed for PFC induction. Differentiation was induced by spleen cells from SRbc primed 2a4b mice in the presence of SRbc or ChRbc but not rabbit or human erythrocytes. Activity was depleted by treatment of the spleen cells with anti-Thy-1 or anti-Lyt-1 but not anti-Lyt-2 plus complement. Helper cells could also be induced by priming 2a4b mice with ChRbc but not rabbit or human Rbc. Neither of these last two would induce differentiation of CH12, even when both homologous antigen and SRbc were present in the cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Induced differentiation of a B cell lymphoma with known antigen specificity. 624 57

The mechanisms of the suppressive activity of spleen cells from mice undergoing a graft-vs-host reaction (GVH) to non-H-2 histocompatibility Ag were investigated. In our model GVH is induced by injecting bone marrow and spleen cells from B10.D2 (H-2d Mlsb) donors into lethally irradiated (DBA/2 x B10.D2)F1 (H-2d/d Mlsa/b) recipients that differ only with regard to non-H-2 Ag. GVH spleen cells inhibit the mitogenic responses to Con A and LPS, as well as the anti-bromelain-treated mouse RBC (Br-MRBC) antibody response. This suppression was nonspecific and non-H-2-restricted and was not modified after treatment with anti-Thy-1 plus C. Conversely it was abrogated after treatment with L-leucyl methyl ester. These features permitted the identification of non-T cell, L-leucyl methyl ester-sensitive, cells involved in this type of suppression. The suppression mediated by GVH spleen cells was linked to the activity of IFN-gamma and transforming growth factor-beta 1 (TGF-beta 1) (TGF-beta 1 was found to be synthesized by GVH spleen T cells). mAb to IFN-gamma abrogated the suppression of the mitogenic response to Con A and the anti-Br-MRBC response and slightly reversed the suppression of the mitogenic response to LPS. Anti-TGF-beta 1 antibody partially abrogated the suppression of the mitogenic response to LPS and totally abrogated that of the anti-Br-MRBC response but left unmodified the suppression of the mitogenic response to Con A. These results are discussed within the framework of the mechanisms underlying the immunosuppression associated with GVH.
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PMID:Involvement of IFN-gamma and transforming growth factor-beta in graft-vs-host reaction-associated immunosuppression. 845 Feb 27


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