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)

A monoclonal antibody was developed against an 8,000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-gamma, tumor necrosis factor, or interleukin 1 alpha or 1 beta. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes.
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PMID:A peptide secreted by human alveolar macrophages releases neutrophil granule contents. 368 Sep 45

The levels of class II major histocompatibility complex (MHC) antigens (la antigens) on cells of a cultured B lymphoma line (WEHI-279) were significantly increased after 24 hr incubation with medium conditioned by concanavalin A-stimulated mouse or rat spleen cells, or by an azobenzenearsonate- (ABA) specific T cell clone that had been stimulated with ABA-coupled spleen cells or concanavalin A. The levels and properties of the la-inducing activity correlated with those of interferon-gamma (IFN-gamma) measured by inhibition of virus plaque formation. Both the la-inducing activity and the IFN-gamma from the T cell clone had an apparent m.w. of 40,000 determined by gel filtration, were sensitive to treatment with trypsin or exposure to pH 2, but were stable to heat (56 degrees C, 1 hr). The induction of la antigens on WEHI-279 cells was dose-dependent, and the maximum response occurred at a concentration corresponding to 1 to 2 U/ml of antiviral activity. This T cell-derived IFN-gamma-like molecule also increased the expression of cell surface la antigens on another B cell line (WEHI-231), and cell lines of macrophage (J774) and myeloid (WEHI-3B and WEHI-265) origin. Furthermore, in all cases the levels of class I MHC (H-2K or H-2D) antigens were also increased. Similar patterns of induction of Ia and H-2 antigens were obtained with supernatants containing IFN-gamma produced by a monkey cell line (COS) that had been transfected with a plasmid bearing the cloned murine IFN-gamma gene. This activity was sensitive to pH 2 and was not present in the supernatant from COS cells that were not transfected with the murine IFN-gamma gene. These results established that IFN-gamma is the T cell-derived molecule that induces the enhanced expression of Ia and H-2 antigens on B cells and macrophages. A major physiologic role of IFN-gamma may be to regulate immune function through the enhanced expression of MHC antigens.
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PMID:Interferon-gamma induces enhanced expression of Ia and H-2 antigens on B lymphoid, macrophage, and myeloid cell lines. 640 89

Certain properties of the antirickettsial activity and interferon in lymphokine preparations obtained from concanavalin A-stimulated mouse spleen cells were compared. Both the antirickettsial activity and interferon were relatively stable to heating at 56 degrees C, whereas both activities were destroyed by trypsin, by heating at 80 degrees C, or by exposure to pH 2 for 24 h. Both activities were likewise inhibited after incubation with rabbit antisera to partially purified murine interferon-gamma. In contrast to the mouse lymphokine preparations, which contained both interferon-gamma and antirickettsial activity, a preparation of virus-induced interferons (type I) had no detectable antirickettsial activity. Human foreskin fibroblasts, which were not sensitive to the antirickettsial activity in mouse lymphokines, acquired the ability to inhibit rickettsial growth when they were cocultured with sensitive mouse L929 cells treated with mouse lymphokines. These results are consistent with the idea that the antirickettsial activity in mouse lymphokines is due to interferon-gamma.
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PMID:Comparison of the properties of antirickettsial activity and interferon in mouse lymphokines. 641 12

Supernatants harvested from concanavalin A-stimulated human peripheral mononuclear cells after 24 hr of incubation contain one interferon species similar to human interferon-gamma (IFN-gamma) with a pI of 4.6-5.3 (first day pH 5 IFN-gamm). In contrast, during the subsequent 24 hr of incubation two species with properties of IFN-gamma are produced with pI of 3.6-4.0 (second day pH 4 IFN-gamma) and 4.6-5.6 (second day pH 5 IFN-gamma), respectively. First day pH 5 IFN-gamma and second day pH 5 IFN-gamma have been found to differ on the basis of trypsin sensitivity. This pattern of polymorphism is similar to the pattern previously described for human migration-inhibitory factor (MIF) which can be separated into first day pH 5 MIF, second day pH 3 MIF, and second day pH 5 MIF. However, IFN-gamma-like species can be differentiated from MIF biochemically and antigenically. Fractions with second day pH 4 IFN-gamma have no MIF activity and fractions with second day pH 3 MIF contain no IFN activity. In addition, first and second day pH 5 MIF, which also contain IFN-gamma activity, can be separated from the latter by precipitation as well as neutralization with polyclonal and monoclonal anti-human MIF antibodies.
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PMID:Dissociation of human interferon-gamma-like activity from migration-inhibition factor. 643 88

The role of mast cells in provoking immediate-type hypersensitivity reactions is well established, but their involvement in chronic inflammation and immune reactions is not so clear. Mast cells synthesize and secrete large amounts of active proteinases, including tryptase, chymase, carboxypeptidase and cathepsin G, which can rapidly process numerous biologically active peptides and proteins or their precursors. Furthermore, mast cells are able to produce a variety of cytokines such as interleukin-4 (IL-4), IL-5, IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) which are known to be intensively involved in modulating and directing inflammatory responses in the skin. In this review, the role of mast cell proteinases and cytokines in skin inflammation is discussed.
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PMID:Mast cell proteinases and cytokines in skin inflammation. 772 38

CD6, a type I cell surface glycoprotein expressed predominantly by thymocytes and mature T lymphocytes, becomes phosphorylated on tyrosine residues following T cell activation and has been implicated as an accessory molecule in T cell activation. The purpose of this study was to identify cell lines and tissues which express CD6 ligand(s), determine the requirements for CD6 binding, and biochemically characterize the putative CD6 ligand(s). Binding studies with a CD6 immunoglobulin fusion protein, CD6-Rg, allowed the identification of a number of human cell lines which express a CD6 ligand(s). The binding to these cell lines was trypsin sensitive, in part required divalent cations, was blocked by an anti-CD6 mAb, and could be downregulated by tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Among the cell lines tested, the human breast carcinoma-derived cell line HBL-100 expressed the highest levels of CD6 ligand(s) and was used for immunoprecipitation studies. Following metabolic labeling, CD6-Rg immunoprecipitated glycoproteins of approximately 100, approximately 90, and approximately 45 kDa from HBL-100 cells. Using CD6-Rg we were able to show that murine thymus, lymph nodes, and skin express high levels of CD6 ligand(s) and that CD6-Rg bound to a murine thymic epithelial cell line and to cultured human epidermal keratinocytes.
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PMID:Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues. 792 88

In the pathogenesis of sparganosis, proteases have been considered to play important roles in tissue migration and parasite feeding. Several bands of proteolysis were observed when crude extracts of Spirometra mansoni plerocercoid (sparganum) were examined using gelatin substrate gel at neutral pH, of which two proteases of 198 and 104 kDa were purified by two chromatographic steps, and a 36 kDa protease was purified by gelatin-affinity and DEAE-anion exchange chromatography. All the purified proteases exhibited optimal activity at pH 7.5 and 0.1 M Tris-HCl. Proteolytic activities at 198 and 104 kDa were inhibited specifically by serine protease inhibitors and 4-(amidinophenyl)methanesulfonyl fluoride (APMSF, 0.5 mM) and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK, 1 mM), which strongly suggested that these two proteases were trypsin-like proteases. The activity of the 36 kDa protease was inhibited by N-tosyl-L-phenylalanine chloromethyl ketone (TPCK, 1 mM) and chymostatin (0.1 mM), and was potentiated in 10 mM Ca2+ which showed that the protease had a chymotrypsin-like property. All the proteases were Schiff (PAS) positive. Proteases of 198 and 104 kDa degraded collagen completely within 24 h. The 36 kDa enzyme cleaved human recombinant interferon-gamma (rIFN gamma) and bovine myelin basic protein. In addition, all the purified proteins elicited strong antibody responses in the infected patients.
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PMID:Characterization of three neutral proteases of Spirometra mansoni plerocercoid. 802 61

Expression of a mast cell tryptase mRNA was detected in two human monocytic cell lines, the U-937 and the Mono Mac 6, and in normal human peripheral blood (PB) monocytes. In the U-937 cell line but not in normal PB monocytes, the tryptase expression was upregulated 3-50 fold following phorbol ester (PMA)-induced differentiation, but no such induction was seen after retinoic acid, interferon-gamma or vitamin D3 exposure. The tryptases expressed in PMA-induced and non-induced U-937 and in Mono Mac 6 were characterized by PCR amplification and nucleotide sequence analysis. The U-937 cell line was found to express a tryptase identical to one of the previously cloned mast-cell beta tryptases (Tryptase I), and the tryptase expressed in Mono Mac 6 was found to be nearly identical to the previously cloned alpha tryptase. By northern blot analysis with oligonucleotide probes specific for the alpha and beta tryptases both cell lines were found to express only one type of tryptase. Densitometric quantifications of tryptase mRNA levels, in the two cell lines, showed approximately 80 times higher mRNA levels in Mono Mac 6 compared to non-induced U-937. Immunohistochemical staining for tryptase showed a marked heterogeneity in the Mono Mac 6 cell line. Only one out of 10 cells were positive for the protein but the levels in these cells were very high, equivalent, or even higher than the levels seen in the human mast cell line HMC-1. This shows that the expression of a single tryptase, in this case the alpha tryptase, is sufficient for the production of a stable protein and probably also a stable proteolytically active tetramer. The family of human mast-cell tryptases has been considered to represent a class of proteases specifically expressed in mast cells and basophilic leucocytes. The expression of tryptases in two monocytic cell lines and in normal PB monocytes indicate that in humans, the lineage specificity of these serine proteases is less restricted than earlier expected. The cloning of a full length cDNA for the murine counterpart to the human mast cell tryptases, the MMCP-6, is presented. No expression of the MMCP-6 was detected in a panel of mouse monocyte or macrophage cell lines indicating a species difference in the lineage specificity of the 'mast cell tryptases'.
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PMID:Expression of a mast cell tryptase in the human monocytic cell lines U-937 and Mono Mac 6. 821 Sep 98

A population of cells enriched for pulmonary interstitial macrophages was obtained by differential adherence of lung parenchymal cells released by dissociation with trypsin. These cells secreted a molecule or molecules that bound to epidermal growth factor (EGF) receptors expressed on pulmonary fibroblasts. Secretion was reproducibly stimulated by exposure of the macrophages to interferon-gamma. Binding to EGF receptors could be blocked by a polyclonal antibody to EGF. It could also be partially blocked by incubation with heparin, suggesting that at least a component of the activity might be due to a member of the heparin-binding subgroup of the EGF family of growth factors. Because pulmonary fibrosis is consistently associated with inflammatory accumulation of activated T-lymphocytes, induction by interferon-gamma of growth factor secretion by macrophages could have pathogenetic importance. We speculate that similar cellular interactions may play a role in the progression of other chronic inflammatory lesions to fibrosis.
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PMID:Secretion of epidermal growth factor-like molecular species by lung parenchymal macrophages: induction by interferon-gamma. 827 99

Previous studies in many laboratories have shown that macrophage Ia expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures induce blood monocyte Ia expression as demonstrated by immunofluorescence. This process is time-related and is also dependent on novel protein synthesis, being abrogated when the monocytes are pretreated with cycloheximide. Preliminary characterization shows the mesangial cell product to be sensitive to heating at 100 degrees C x 30 min, to be resistant to digestion by trypsin at a concentration of 4 x 10(-6) M, and to have a molecular size of 10-100 kD as established by Amicon ultrafiltration. The substance is not interferon-gamma (IFN-gamma) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no detectable levels of IFN-gamma, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monocytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-gamma. Similarly, experiments using anti-CSF-1 have excluded the possibility that the substance is CSF-1. The results of the study have relevance to the mechanisms by which monocytes which take up residence in the glomerular mesangium acquire Ia positivity, and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.
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PMID:Induction of mouse monocyte Ia expression by a mesangial cell-derived product. 842 98


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