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)

From our experiments and those of others in which cells were cultured at a density of 100,000 cells per well, it has been suggested that autoantibody production against mouse bromelain-treated erythrocytes (mouse brom-RBC) was independent of T cells, and further, was enhanced by the removal of T cells from responsive cell populations. Here it is shown in limiting dilution cultures that the autoimmune response is highly dependent on T cells or their products. B cells purified from the peritoneal cavities of untreated mice did not differentiate in vitro into autoantibody-secreting cells unless provided with signals from at least one of two types of accessory cells. These were plastic adherent cells and T cells, derived either from the peritoneal cavity or from established cell lines. Here it is shown that peritoneal T cells or T cells from the LBRM-33 cell line stimulated the differentiation of purified B cells in vitro in the absence of added mitogens. The accessory cell effect could be transferred in supernatants derived from T-cell cultures but not filler-cell cultures. Recombinant interleukin-2 (rIL-2) added to culture medium did not stimulate B cells directly, but could increase precursor frequencies when added to unfractionated peritoneal cell cultures, or B-cell cultures to which cells from a T-cell line had been added. From these results, it is concluded that the differentiation of precommitted peritoneal B cells in vitro into autoantibody secretors is at least partially dependent on T cells or lymphokines derived from them. Therefore, any proposed mechanisms for regulation of this autoimmune response should encompass the requirement for T cells or their products in the final differentiation stages to autoantibody secretion.
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PMID:T cells or their products are required for the differentiation of precursor B cells into antibody-secreting cells specific for a supposed T-independent self-antigen. 349 70

Lymphocytes constitute a critical component of host defenses against cryptococcosis. Previously, we demonstrated that human lymphocytes cultured with interleukin-2 formed conjugates with, and directly inhibited the growth of, Cryptococcus neoformans. Here, we explore the anticryptococcal activity of freshly isolated, highly purified populations of human peripheral blood lymphocytes. Lymphocytes were incubated with encapsulated C. neoformans for 24 h, after which the lymphocytes were lysed, dilutions and spread plates were made, and CFU were counted. Fungistasis was determined by comparing growth in wells with and without lymphocytes. Nylon wool-nonadherent peripheral blood mononuclear cells (NWNA PBMC) were highly fungistatic, even if either T cells or natural killer (NK) cells were depleted by panning. A mixed population of T cells and NK cells, obtained by rosetting NWNA PBMC with sheep erythrocytes, completely inhibited cryptococcal growth, whereas the nonrosetting cells had little fungistatic activity. CD4+, CD8+, and CD16/56+ lymphocytes, isolated by positive immunoselection, had potent growth-inhibitory activity. In contrast, purified B cells had no activity. Fungistasis was seen even in the absence of opsonins. Antifungal activity was markedly diminished when surface receptors on NWNA PBMC were cleaved by treatment with trypsin or bromelain. Supernatants from stimulated lymphocytes or concentrated lymphocyte sonicates were not active. Lymphocyte-mediated fungistasis was seen with two different strains of C. neoformans. CD4+, CD8+, and CD16/56+ lymphocytes formed conjugates with C. neoformans, as observed under Nomarski differential interference contrast microscopy and videomicroscopy. These data demonstrate that freshly isolated peripheral blood T cells and NK cells have the capacity to bind and directly inhibit the growth of C. neoformans.
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PMID:Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. 826 27

Bromelain, a crude extract from pineapple stem containing various thiol proteases, has previously been suggested for adjuvant therapy of malignant diseases. We hence tested in vitro whether a highly purified bromelain proteinase (F9) would affect the antitumor activity by human peripheral blood lymphocytes (PBL) against MCF-7 breast cancer, KB squamous carcinoma and SK-MEL-28 melanoma cells. The antiproliferative effects by pretreated PBL were determined using the microculture tetrazolium (MTT) assay. All three cell lines were susceptible to F9-treated PBL and KB cells were selected to examine the kinetics, the dose dependency and the specificity of the F9 effects on PBL. Maximal antitumor effects were obtained when PBL were incubated with 25 mug/ml of F9 for 3 days at which the proteolytical activity of the added F9 was 1.6 U/mg. The F9-induced PBL antitumor activity was dependent on the applied proteolytical activity and abolished when F9 was inactivated by iodoacetamide. In contrast to F9, trypsin or pronase were not able to induce PBL-mediated growth inhibition of KB target cells. In response to F9, the concentration of interleukin-2 (IL-2) and tumor necrosis factor-a increased 10 and 19 fold in the PBL supernatant, respectively. F9 was found to synergize LAK cell activity in addition to suboptimal concentrations (0.625-2.5 U/ml) of rIL-2. In contrast to rIL-2-activated PBL, no cytolytic effect by F9-activated PBL was measured in the BCECF release assay, suggesting that F9 acts by a mechanism different from that of IL-2. F9 was also found to be growth inhibitory in the MTT assay, when it was directly added to the tumor cells: The concentration, at 50% growth inhibition by F9, was in the range of 25-38 mug/ml at which the proteolytical activity of the added F9 was 2.5 U/mg. On the basis of the present study we suggest that F9 alone, or in combination with rIL-2, may be used as a potential biological response modifier in specific immunotherapy of distinct cancer diseases.
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PMID:Bromelain proteinase-f9 augments human lymphocyte-mediated growth-inhibition of various tumor-cells in-vitro. 2155 75