Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteolytic events might play a role during lymphocyte activation. Mouse spleen cells were therefore stimulated in serum-free cultures by PHA, ConA, LPS and dextran sulphate and the effect of various added protease inhibitors on [3H]-thymidine incorporation investigated. Both soybean inhibitor and Trasylol inhibited the response of the cells to all mitogens. The other inhibitors (antipain, leupeptin, ovomucoid, alpha-1 trypsin, alpha-2 macroglobulin) had little or no effect. The marked inhibitory effect of tosyl-lysine chloromethylketone could be neutralized by reduced glutathione, indicating an effect on intracellular glutathione rather than on proteases.
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PMID:Protease inhibitors reduce mitogen induced lymphocyte stimulation. 8 14

Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatlabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites.
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PMID:Effect of leukocyte hydrolases on bacteria. XV. Inhibition by antibiotics, metabolic inhibitors, and ultraviolet irradiation of the release by leukocyte extracts, trypsin, and lysozyme of lipopolysaccharide from gram-negative bacteria. 9 59

Normal human serum was shown to inhibit the mitogenic effects of bacterial lipopolysaccharide and Con A on mouse spleen lymphocytes and reduce the in vitro antibody response to SRBC by these cells. Furthermore, it was demonstrated that immune suppression occurred without loss of lymphocyte viability. Fractionation of normal human serum resulted in isolation of several immunoenhancing and immunoinhibitory fractions. Electrophoretic analysis of the immunoinhibitory fractions revealed a complex array of serum proteins. The most prominent proteins on polyacrylamide electrophoresis stained for both proteins and carbohydrate. The heterogeneity of immunoinhibitory fractions were further substantiated by their differential susceptibility to trypsin, periodate, and 2-mercaptoethanol treatment. Heterogeneity of the fractions was also shown to be related to difference in their biologic activity as expressed in their effects on mitogenicity and immunogenicity of LPS in mouse splenic cultures. This study lends evidence to the consideration that normal human serum contains several immunoregulatory factors with differing biochemical characteristics and cellular sites of action.
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PMID:Isolation and characterization of immunoregulatory factors from normal human serum. I. Preliminary biochemical and biological characterization of immunosuppressive factors. 19 Mar 15

Spleen cells from adult mice were rendered "tolerant" to TNP by exposing cells in vitro to large concentrations of TNP10BSA. After such treatment the residual response to TNP was measured using TNP-LPS as antigen in vitro or in vivo. The "tolerance" observed in this system was not reversed by treating the cells with trypsin, nor by using non-specific polyclonal activators. Furthermore, responsiveness to TNP-LPS in vitro was not substantially restored when such "tolerant" cells were "parked" in vivo for 7 days. In contrast when TNP-KLH was the antigen used to challenge TNP-BSA treated cells, no unresponsiveness was observed. The results are discussed in terms of the degree of thymus dependence of the challenge antigens; subpopulations of B cells, and current hypotheses of B-cell activation;
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PMID:Can B-cell tolerance be induced by oligovalent thymus dependent antigens? 30 Nov 14

Tumor culture toxohormone (TCT) obtained from cultures of MBQA mouse tumor cells, a line derived from a methylcholanthrene-induced fibrosarcoma (CBA/J origin), suppressed the mitogenic responsiveness of mouse spleen cells (PHA, LPS) as well as the antibody formation to SRBC in vitro. The immunosuppressive activity of toxohormone was readily inactivated by heating at 100 degrees C or treatment with trypsin, but not by DNase and RNase treatment.
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PMID:Immunosuppression induced by "toxohormone" from mouse tumor cells in culture. 49 45

3H-Thymidine uptake of thymocytes from LPS-responder Balb/c mice in the presence of a submitogenic dose (0.5 microgram/ml) of con A in vitro was significantly enhanced by adding LPS (0.1 to 2.5 microgram/ml), while the uptake of thymocytes from LPS-nonresponder C3H/HeJ was not enhanced by LPS. However, "endotoxin soups," which were prepared from the supernatants of LPS-responder murine spleen cell cultures in the presence of LPS, clearly increased the incorporation of 3H-thymidine into C3H/HeJ thymocytes in the presence of this small amount of con A. The soup prepared from C3H/HeJ spleen cell cultures did not show any synergistic effect with con A. Even if the major histocompatibility between soup-producer cells and responder cells to con A was different, the soups were still effective. The active substance in the "endotoxin soups" was eluted through a Sepharose CL-4B column, and its molecular size was estimated to be about 20,000 daltons. The activity of the soups was destroyed by heating at 70 C for 30 min or at 80 C for 10 min. Digestion with trypsin destroyed the activity of the soups, but digestion with DNase or RNase did not. The role of the active substance in the soups in synergy with con A and its relation to the synergistic effect of con A and LPS are discussed.
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PMID:Lipopolysaccharide-induced mediators assisting the proliferative response of C3H/HeJ thymocytes to concanavalin A. 53 Jan 3

C3a, C3b, C3c, and C3d were generated from purified guinea pig C3 by trypsin treatment. These fragments were characterized immunochemically and functionally by rosette inhibition. C3b is capable of binding to both C3b and C3d receptors on lymphocytes whereas C3d binds only to C3D receptors. C3b stimulates guinea pig spleen cells to elaborate a macrophage chemotactic factor which is similar in m.w. to that generated in response to PHA or LPS and is antigenically unrelated to C3 or C5. In contrast, neither C3a, C3c, or C3d stimulate guinea pig lymphocytes. Neither C3 nor any of its major fragments induce cellular proliferation. These data are compatible with the hypothesis that C3b triggers spleen cells to release a macrophage chemotactic factor by cross-linking C3b and C3d receptors.
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PMID:Interaction of soluble C3 fragments with guinea pig lymphocytes. Comparison of effects of C3a, C3b, C3c, and C3d on lymphokine production and lymphocyte proliferation. 93 30

Two neutral proteinases from human polymorphonuclear leukocytes (PMN), an elastase and the chymotrypsin-like cathepsin G, were purified, and their actions on lymphocytes in culture were studied. Both PMN proteinases stimulate lymphocytes from human peripheral blood and from mouse spleen in vitro, but do not affect thymic cells from either normal or hydrocortisone-treated mice. In stimulated mouse spleen cell cultures, most of the developing blast cells bear surface immunoglobulins, and subsequently appear to engage in antibody synthesis. In their stimulatory action, the two PMN proteinases thus resemble the classic B-cell mitogen LPS and neutral pancreatic proteinases such as trypsin, chymotrypsin, and elastase. The effects of proteinase inhibitors indicate that lymphocyte stimulation is dependent on the proteolytic activity of the enzymes. This work suggests that PMN proteinases, which are released at sites of inflammation, may modulate the function of lymphocytes.
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PMID:In vitro stimulation of lymphocytes by neutral proteinases from human polymorphonuclear leukocyte granules. 97 37

Dextran given to mice caused splenic T cells to elaborate factors in vitro which heightened normal splenic B- and T-cell responses to the mitogens LPS and Con A, respectively. Chromatographic separation of dextran-triggered spleen cell supernatants revealed two T cell-derived enhancing factors which affect T cells (TDEF-TI and TDEF-TII) and two that alter B cells (TDEF-BI and TDEF-BII). All appear to be proteinaceous because exposure to trypsin destroyed their activities. Furthermore, their presence was found to be dependent upon protein synthesis since cycloheximide treatment of the cells inhibited synthesis whereas mitomycin C treatment did not. Based on absorption studies, receptors for TDEF-TI and TII were detected on thymic cells as well as on O-deficient bone marrow cells, whereas receptors for TDEF-BI and BII were on bone marrow cells but not thymic cells.
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PMID:Characterization of dextran-activated T-cell factors. 108 53

Murine lymphocytes from spleen, lymph node, and thymus were examined for IgM complex receptors. Lymphocytes from all three organs were found to bind SRBC sensitized with IgM from various sources including: primary anti-SRBC serum, murine and rabbit anti-Escherichia coli LPS sera, and a murine IgM myeloma (MOPC 104E). Rosette formation by lymphocytes with IgM-sensitized SRBC was inhibited by soluble antigen-IgM complexes but not by IgM or antigen alone. Rosette formation was also inhibited by human IgM (Fc)5mu but not by Fab mu. Antiserum and complement treatment of the cells and subsequent recovery of the viable cells by trypsinization, filtration, and washing revealed the IgM rosette-forming cell (RFC) in the thymus to be a T cell. Spleen on the other hand was found to contain both B and T cells capable of binding IgM sensitized SRBC. Removal of both B and T cells from spleen cell suspensions eliminated all IgM RFC. The IgM complex receptor was found to be trypsin insensitive. Anti-Ig column fractionation enriched IgM RFC in spleen and lymph node suspensions passed through the columns, whereas cells bearing surface Ig, IgG complex receptors, and C3 receptors were retained in the columns.
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PMID:IgM complex receptors on subpopulations of murine lymphocytes. 108 66


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