Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmin reacted readily with recombinant murine interferon-gamma (rIFN-gamma) in vitro, reducing the relative molecular mass of each monomer by approximately 1,000. The amino terminus of the rIFN-gamma remained intact and no sites of internal peptide bond hydrolysis were detected, indicating that the plasmin target region is most likely near the carboxyl terminus. Cleavage of rIFN-gamma was observed with similar concentrations of trypsin or min-plasmin. By contrast, human neutrophil elastase failed to alter the structure of rIFN-gamma. The plasma proteinase inhibitor, alpha 2-antiplasmin, protected rIFN-gamma from plasmin digestion. Purified alpha 2-macroglobulin-plasmin complex cleaved rIFN-gamma; however, the activity was greatly reduced compared with the free proteinase. The antiviral activity of the rIFN-gamma was enhanced four- to fivefold by treatment with plasmin or trypsin. By contrast, naturally occurring murine IFN-gamma was inactivated by plasmin (80%), suggesting that the effect of plasmin on IFN activity can vary depending on the preparation studied. The importance of plasmin at the site of an immune reaction is well established. This investigation identifies plasmin and miniplasmin as physiologic proteinases capable of reacting with IFN-gamma in vivo.
...
PMID:Cleavage of recombinant murine interferon-gamma by plasmin and miniplasmin. 252 20

We have identified a late, committed stage in the differentiation of the mast cell progenitor just before granulation. Mast cell committed progenitors (MCCP) are nongranulated cells with a density of 1.060 to 1.070 g/ml which can be harvested from the mesenteric lymph node of mice infected with Nippostrongylus brasiliensis. Mast cell-committed progenitors are able to proliferate and differentiate in the absence of IL-3 or IL-4 when cultured on a monolayer of embryonic skin or 3T3 fibroblasts and can form colonies in methylcellulose supplemented with fibroblast conditioned medium. Fibroblast conditioned medium appears to contain a soluble MCCP proliferation factor that maintains biologic activity when heated to 56 degrees C for 45 min but is destroyed by incubation with either trypsin or chymotrypsin. It can be selectively precipitated with 60 to 70% saturated ammonium sulfate. The factor is not absorbed by immobilized antibodies to nerve growth factor. The MCCP proliferation activity of the factor could not be mimicked by IL-1, IL-2, IL-4, granulocyte-macrophage-CSF, granulocyte-CSF, macrophage-CSF, IFN-alpha/beta, IFN-gamma, nerve growth factor, epidermal growth factor, serum fibronectin, heparin, or a number of glycosaminoglycans. At high salt concentrations, the factor passes through a 50-kDa membrane and can be concentrated above a 5-kDa membrane. MCCP acquire a connective tissue phenotype when cultured on a fibroblast monolayer and a mucosal phenotype when cloned in the presence of conditioned medium from PWM-stimulated spleen cells. When cultured in the absence of IL-3 on a monolayer of embryonic skin or 3T3 fibroblasts, mast cell-committed progenitors produce mast cells which stain with berberine sulfate suggesting a connective tissue phenotype; however, the mast cells that develop when mast cell-committed progenitors are cultured in the presence of IL-3 or conditioned media from PWM-stimulated spleen cells do not stain with berberine sulfate. MCCP intercalate into monolayers of embryonic skin or 3T3 fibroblasts, but T cells are not able to associate with the monolayer and can be completely washed away. Attempts to enrich mast cell-committed progenitors by intercalation and elution from embryonic skin monolayers proved unsuccessful, but some enrichment of mast cell-committed progenitors could be achieved by discontinuous Percoll gradients. Thus, we have identified a way to obtain late-stage, mast cell-committed progenitors in an environment that is virtually uncontaminated with other hematopoietic progenitors.
...
PMID:The mast cell-committed progenitor. I. Description of a cell capable of IL-3-independent proliferation and differentiation without contact with fibroblasts. 278 62

Radioiodinated recombinant human interferon-gamma (IFN gamma) bound to human monocytes, U937, and HL60 cells in a specific, saturable, and reversible manner. At 4 degrees C, the different cell types bound 3,000-7,000 molecules of IFN gamma, and binding was of comparable affinity (Ka = 4-12 X 10(8) M-1). No change in the receptor was observed after monocytes differentiated to macrophages or when the cell lines were pharmacologically induced to differentiate. The functional relevance of the receptor was validated by the demonstration that receptor occupancy correlated with induction of Fc receptors on U937. Binding studies using U937 permeabilized with digitonin showed that only 46% of the total receptor pool was expressed at the cell surface. The receptor appears to be a protein, since treatment of U937 with trypsin or pronase reduced 125I-IFN gamma binding by 87 and 95%, respectively. At 37 degrees C, ligand was internalized, since 32% of the cell-associated IFN gamma became resistant to trypsin stripping. Monocytes degraded 125I-IFN gamma into trichloroacetic acid-soluble counts at 37 degrees C but not at 4 degrees C, at an approximate rate of 5,000 molecules/cell per h. The receptor was partially characterized by SDS-polyacrylamide gel electrophoresis analysis of purified U937 membranes that had been incubated with 125I-IFN gamma. After cross-linking, the receptor-ligand complex migrated as a broad band that displayed an Mr of 104,000 +/- 18,000 at the top and 84,000 +/- 6,000 at the bottom. These results thereby define and partially characterize the IFN gamma receptor of human mononuclear phagocytes.
...
PMID:Demonstration and partial characterization of the interferon-gamma receptor on human mononuclear phagocytes. 293 8

Previously it was shown that macrophages (M phi) isolated from the vigorous (Vig) or modulated (Mod) liver granulomas (Gr) of Schistosoma mansoni-infected mice restored mitogen and parasite egg antigen-induced proliferative responses to accessory cell-depleted lymphocytes. Furthermore, supraoptimal concentrations of highly activated VigGrM phi suppressed lymphoproliferation to a greater extent than did the lesser activated ModGrM phi. In this study we investigated the role of soluble mediators in GrM phi accessory/regulatory activity. Indomethacin released VigGrM phi-mediated inhibition of mitogen but not antigen-induced lymphoproliferation. Extensively dialyzed serum-free GrM phi culture supernatant nonspecifically suppressed SEA- or KLH-induced blastogenesis. Culture supernatants also reduced vesicular stomatitis virus-induced plaque formation in supernatant-pretreated L-929 fibroblasts. The 20 to 45 Kd GrM phi-derived lymphoproliferation suppressive factor (SF) and the 20 to 50 Kd viral plaque-reducing factor (PRF) were stable at low pH, but became inactivated by heat and trypsin digestion. Although freshly isolated Vig or ModGrM phi contained preformed SF and PRF, in vitro production of the factors were depressed by protein synthesis inhibitors. Moreover, SF was active only when added to cultures before day 3 of the 6-day proliferation assay. Both SF and PRF were specifically retained on rabbit anti-murine IFN-alpha/beta immunoaffinity columns. Thus, the suppressive activity of Vig or ModGrM phi is in part mediated by a monokine that shares physical, biological, and antigenic characteristics with murine IFN-alpha/beta. In contrast to the suppression of antigen-driven proliferation, GrM phi culture supernatant costimulated PHA-induced mitogenesis. The 13 to 21 Kd GrM phi-derived lymphocyte-activating factor (LAF) was stable to heat, low pH, and trypsin digestion. Freshly isolated Vig or ModGrM phi contained preformed LAF, although its in vitro production was depressed by protein synthesis inhibitors. The physical and biological characteristics of GrM phi-derived LAF appear similar to IL 1. It is concluded that both Vig and ModGrM phi secrete regulatory/accessory monokines that may contribute to the initiation and maintenance of the focal inflammatory granulomatous response.
...
PMID:Characterization of regulatory (interferon-alpha/beta) and accessory (LAF/IL 1) monokine activities from liver granuloma macrophages of Schistosoma mansoni-infected mice. 310 71

In the present study we investigated some of the physicochemical properties of macrophage-activating factor(s) (MAF) produced by the tumor-immune Lyt-1+2- T cell subset. Supernatant from mixed culture of spleen and lymph node cells, obtained from C3H/HeN mice immunized with syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma, with the corresponding tumor cells exhibited the capability of activating peritoneal exudate macrophages to exert their cytostatic and cytolytic activities on tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 antibody plus complement (C) before culturing. Anti-Lyt-2.1 and/or anti-asialo GM1 plus C treatment, however, had only marginal effect on the generation of MAF by these cells, despite the complete disappearance of natural killer (NK) cell activity of spleen and lymph node cells after the treatment with anti-asialo GM1 plus C. Thus, the tumor-specific Lyt-1+2- T cell subset could fulfill a crucial role in generating MAF without the support of NK cells. The MAF activity was heat, acid, and trypsin sensitive. On Sephacryl S-300 column, MAF activity was eluated in a broad single peak around a molecular weight (m.w.) of 70,000 daltons. Antiviral activity was detected in the concentrated pool of MAF-containing fractions from Sephacryl S-300. Gel permeation analysis using HPLC also showed a coincident peak of MAF and antiviral activities at a m.w. of approximately 70,000 daltons. In addition, MAF activity was almost completely neutralized by incubation with rabbit antiserum against recombinant murine gamma-interferon (IFN gamma). Taken together, these results indicate that MAF generated by tumor-immune Lyt-1+2- T cell subset is closely related to IFN gamma.
...
PMID:Studies on macrophage-activating factor (MAF) in antitumor immune responses. II. Molecular characterization of MAF produced by the tumor-immune Lyt-1+2- T cell subset. 311 13

Sera from 61 patients with systemic lupus erythematosus (SLE) were serially screened over a period of at least 2 years for IFN and anti-IFN antibodies. IFN concentrations were measured both with a cytopathic effect assay and a more sensitive radioimmunoassay. Of the patients 15% (9/61) had IFN in their serum at one or more occasions as measured in the bioassay (greater than or equal to 6 IU/ml); employing a RIA (greater than or equal to 1 IU/ml) 28% (17/61) of the patients studied were positive for IFN-alpha. Fifteen patients had a measurable interferonemia over 2-16 months; only two patients had detectable IFN in their serum at only one occasion. In five patients, hourly and daily variations of the IFN titer as measured by RIA were found to amount to less than 80%. The IFN activity found in these sera was characterized as IFN-alpha by means of acid stability, cross-reactivity on heterologous cells, trypsin sensitivity, and neutralization by homologous and heterologous antisera. IFN antibodies were quantified with a neutralization bioassay, an ELISA, and a radioimmunoassay. Of the 61 patients 5% (3) possessed high titers of anti-IFN antibodies which persisted over 2 years. The IFN-alpha antibody positive patients had an inactive form of the disease over years without visceral involvement but decreased serum complement levels (C4, C3, CH50) and repeated episodes of Quincke-like edema.
...
PMID:Presence of interferon and anti-interferon in patients with systemic lupus erythematosus. 326 58

Interferon(IFN) can be produced from lymphocytes in vitro as well as in vivo using various immune stimuli. This paper shows that the amount of IFN or IFN-like substance increases in pregnancy sera as pregnancy proceeds. 1) IFN activity was detected in 45% of 97 pregnant women overall and more frequently as pregnancy went on. 2) The IFN was trypsin sensitive, beat labile, acid sensitive and species specific. 3) Maternal lymphocytes produced approximately twice as much interferon as cord blood lymphocytes did by phytohemagglutinin stimulation. 4) IFN was detected in half of the mixed lymphocyte cultures(MLR) containing cord blood and maternal blood. Whether or not they can produce IFN may be an indication of the immunological competence of pregnant women and the interferon may contribute to the immunoregulation of fetal acceptance.
...
PMID:[Interferon-like substance in pregnancy sera]. 619 Sep 68

Murine fibroblast interferon (MuIFN, 90% beta, 10% alpha) was associated with both positively and negatively charged liposomes formed by reverse-phase evaporation. This interferon-liposome association occurred predominantly in a manner that resulted in protection of a significant portion of the IFN's antiviral activity from trypsin digestion, yet also permitted biological expression of this activity without prior liposome disruption. A differential dissociation of antiviral and antimitogenic activities was observed with MuIFN associated with positively vs negatively charged liposomes, as reflected by differential sensitivities to trypsin inactivation. This may reflect either (1) differential associations of various molecular species of MuIFN with liposomes, or (2) that different portions of the IFN molecule are responsible for the antiviral and the antimitogenic activities.
...
PMID:Partial dissociation of antiviral and antimitogenic activities of murine interferon after its incorporation into liposomes. 619 85

To clarify the co-expression phenomenon of T-cell Fc receptors (FcR) specific for different isotypes on the clonal level, a murine hybridoma clone T2D4 was studied. T2D4 cells originally reported to bear FcR for IgG (Fc gamma R) and to release a Fc gamma R-related T-cell factor binding to IgG (immunoglobulin binding factor; IBF) proved to have also the receptor for IgA. The binding of IgA was detected by rosette formation with trinitrophenylated ox red blood cells (TNP-ORBC) after preincubation of T2D4 cells with MOPC 315 IgA having anti-TNP activity, or directly with TNP-ORBC sensitized with MOPC 315 IgA. While the binding of MOPC 315 IgA was competed for by IgA but not by IgG2A nor IgG2B, IgA failed to inhibit the rosette formation of the cells with ORBC sensitized with rabbit IgG antibody (EA ox gamma), proving that T2D4 cells express FcR specific for IgA (Fc alpha R) in addition to Fc gamma R. Co-expression of both receptors on the same cell surface was demonstrated by a double rosette technique using TNP-quail red blood cells (TNP-QRBC) and EAox gamma. Fc alpha R activity of the cells was completely abrogated by 15 min. incubation with 0.1 mg/ml trypsin, whereas Fc gamma R was resistant even to 1 mg/ml trypsin. The expression of Fc alpha R was augmented (up-regulation) by IgA at the concentration above 300 micrograms/ml and inhibited (down-regulation) by 1000 u./ml of murine beta-interferon (beta-IFN). Conversely, the expression of Fc gamma R was down-regulated by IgA and up-regulated by alpha-IFN. Thus, Fc gamma R and Fc alpha R are co-expressed and reciprocally regulated on these cell lines. The possible co-production of IBF and the Fc alpha R-related binding factor specific for IgA is discussed.
...
PMID:T-cell hybridoma co-expressing Fc receptors for different isotypes. I. Reciprocal regulation of Fc alpha R and Fc gamma R expression by IgA and interferon. 621 65

The binding of iodinated human interferon-alpha 2 (IFN-alpha 2) was studied on the human T cell line, Molt 4. After its initial binding to cells, the IFN is transferred to a trypsin-resistant compartment before appearing in the medium as TCA-soluble material, while the total cell-associated IFN declines to one-third of its maximum value after 3 h incubation. The Na+/H+ ionophore monensin did not prevent intracellular accumulation of IFN but did completely inhibit its breakdown. We interpret our results as evidence for receptor-mediated internalisation of IFN followed by intracellular breakdown.
...
PMID:Kinetics of internalisation and degradation of surface-bound interferon in human lymphoblastoid cells. 624 Nov 48


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---