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 T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to markedly augment T cell activation. To study the activation potential of bromelain-treated CD44 T cells, we have compared the proliferation of sham- and bromelain-treated normal human PBMC to mitogenic CD2 mAb. We found that bromelain not only removed T cell CD44, but also removed the CD45RA isoform of CD45 as well as E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 molecules. T cell proliferation in response to CD2 mAb was increased 325% in bromelain-treated PBMC compared to sham-treated PBMC (p < 0.005). Reciprocal treatment experiments using purified T cells and monocytes demonstrated that the enhancement of T cell CD2 activation by bromelain occurred only when T cells were treated with bromelain and was accompanied by increased adhesion of T cells to monocytes. These data demonstrate that expression of portions of the extracellular domains of the CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules are not required for CD2 activation of human T cells. Rather, the removal of these surface molecules by bromelain is associated with enhanced T cell-monocyte aggregation and enhanced CD2-mediated T cell activation. Taken together with data that CD44, E2/MIC2, CD6, and CD7 mAb inhibit CD2/lymphocyte function-associated Ag-3-mediated cellular interactions and also augment CD2-mediated triggering of T cells, these data suggest that members of the bromelain-sensitive group of surface molecules may comprise a set of CD2-associated adhesion ligands that acts in concert to modulate human T cell activation.
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PMID:Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation. 128 Nov 88

The mechanism of polyclonal B cell activation in autoimmune diseases was investigated by using an autoreactive B cell clone established by somatic hybridization with B cells derived from NZB X NZW (B/W) F1 mice. Briefly, splenic B cells from B/W F1 mice were fused with M12.4.1, a mutant of a B cell line, in the presence of polyethylene glycol and DMSO. NW47.7, a subclone of a resulting hybridoma, expresses B cell surface antigens on the cell membrane, namely IAd, IgM, B220, the receptors for the C3 fragment of complement (C3R), and the Fc portion of IgG (Fc gamma R). It also possesses a receptor molecule for mouse red blood cells treated with bromelain (Br-MRBC) on its surface, by rosette-forming assay with Br-MRBC. In contrast, parental M12.4.1 does not express IAd and IgM on the cell membrane, and does not bind to Br-MRBC under the same conditions. Thus, it is likely that NW47.7 may be an autoreactive B cell clone specific for Br-MRBC. Interestingly, NW47.7 was induced to generate a significant number of IgM-secreting cells when treated with Br-MRBC and rIL-5. Furthermore, mAb against IAd molecules, but not IAk and KdDd, markedly inhibited the differentiative effect of polyclonal activators such as LPS and rIL-5. Also, when MHC identical irradiated B cells were added to the culture of NW47.7 as a stimulator, the induction of IgM-producing cells was greatly augmented, but this augmenting effect was lost by interfering with direct contact of NW47.7 cells with stimulator B cells using a semipermeable membrane, as well as by the addition of mAb against IAd molecules. In addition, irradiated NW47.7, but not M12.4.1, by itself could enhance the secretion of IgM by NW47.7 as a stimulator, but this enhancing effect markedly decreased in the presence of anti-IAd mAb. The present results suggest that surface IA molecules on B cells are involved during the differentiative response to polyclonal activators, and may directly provide a differentiative signal for maturation of B cells into IgM-secreting cells.
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PMID:Functional role of self IA molecules in polyclonal B cell activation using an autoreactive B cell clone derived from (NZB X NZW) F1 mice. 173 10

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

Splenic B cells of BALB/c mice were fused with 2.52M, a mutant of a B cell line, in the presence of polyethylene glycol and dimethyl sulfoxide. AT73.14 a subclone of a resulting hybridoma, expresses B cell surface antigens on the cell membrane, namely IAd, IgM, B220, and receptors for C3 fragment of complement (C3R), the Fc portion of IgG (Fc gamma R), and interleukin 2 (IL-2R). It also possesses a receptor molecule for mouse red blood cells treated with bromelain (Br-MRBC) on its surface, by rosette-forming assay with Br-MRBC. In contrast, parental 2.52M does not express IAd on the cell membrane and does not bind to Br-MRBC on the same conditions. Thus, it is likely that AT73.14 may be an autoreactive B cell clone specific for Br-MRBC. Interestingly, AT73.14 could generate a significant number of IgM-secreting cells when treated with Br-MRBC; this was followed by a marked decrease in the expression of B cell surface markers on the cell membrane. In addition, this differentiative response of the cells greatly augmented in the presence of B151-TRF, a B cell differentiation factor, although B151-TRF alone showed only a marginal effect on the generation of IgM-secreting cells. The result suggests that this kind of an autoreactive B cell clone may provide a good model for the study on the mechanism of autoimmune responses.
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PMID:Establishment of a bromelain-treated isologous red blood cell reactive B cell clone by somatic hybridization. 278 47

MRL/MP-lpr/lpr (MRL/lpr) mice are known to provide a good model for the study on the pathogenesis of systemic lupus erythematosus with massive involvement of abnormal T lymphocytes in the spleen and lymphonodes. However, a direct role of B cells of MRL/lpr mice in autoimmune responses is not clear until this time. In the present study, to investigate the characteristic of B cells of the mice, we tried to establish a B cell clone after hybridization between splenic B cells of these mice and 2.52 M, a HAT selective medium sensitive mutant B cell line in the presence of polyethylene glycol and dimethyl sulfoxide and examined its response to autoantigens. MRL27.4, a subclone of a resulting hybridoma, expressed IgM, B220, IKk, ICAM-1, and LEA-1 on the cell membrane as well as CD5 molecules by analysis with flow microfluorometory (FMF). Also, MRL27.4 was shown to exhibit rosette formation against blood cells treated with bromelain (Br-RBC) at a frequency of more than 95%, and to express DNA-receptor (DNA-R) on its surface by FMF analysis with biotin-labeled ssDNA. In contrast, the parental 2.52 M did not form rosettes with Br-RBC and the expression of DNA-R on the cell membrane of 2.52 M was significantly less compared with that of MRL27.4. Interestingly, MRL27.4 produced a high titer of IgM-anti-ssDNA antibodies and IL-6 after treatment with the purified RBC membrane or immobilized DNA. On the other hand, the parental 2.52 M neither produce IgM-anti-ssDNA antibodies nor IL-6 under the same conditions. The results suggest that MRL27.4 is an autoantigen reactive B cell clone derived from MRL/lpr mice and its surface DNA-R, by itself, function to autoantigens. In this process, there might be an autocrine network mediated by IL-6. In conclusion, MRL27.4 provides a good model for the study on the direct function of B cells of MRL/lpr mice during abnormal immune responses to autoantigens.
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PMID:[Functional analysis of an autoantigen reactive B cell clone derived from MRL/MP-lpr/lpr mice]. 912 24