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)

Alpha-2-macroglobulin (alpha 2M) is a major mammalian plasma proteinase inhibitor and a well-established suppressor of T cell blastogenesis. Its role in modulating T cell-mediated lymphokine production is less well documented. We have isolated and characterized guinea-pig plasma alpha 2M in order to study its role in regulating the elicitation of macrophage agglutination factor (MAggF), a T cell-dependent inflammatory lymphokine closely related to fibronectin. Alpha-2-macroglobulin was purified by a combination of gel chromatography and immunoadsorption to remove contaminating IgM. Purified alpha 2M showed a double band on polyacrylamide gel electrophoresis. It had a molecular weight of 714,000 which fell to 190,000 on reduction, a pI of 4.8 and bound up to 1.3 moles of trypsin or elastase per mole. The elicitiation of MAggF from 25 X 10(6) purified protein derivative (PPD)-stimulated guinea-pig lymph node cells was inhibited 99% by 2-3 micrograms of biologically active alpha 2M only if the proteinase inhibitor was added to the lymph node cells at the same time as antigen. No inhibition of MAggF production was observed when active alpha 2M was added at the end of culture or when biologically inactive alpha 2M was added to the cultures at any time. MAggF was not elicited from normal cells by PPD, nor did alpha 2M have any effect on these cultures. Purified alpha 2M had no direct effect on MAggF activity in culture supernatants. We suggest that alpha 2M may be involved in modulating antigen-elicited lymphokine production in vivo.
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PMID:Regulation of macrophage agglutination factor production by alpha 2-macroglobulin. 619 93

The consumption of alpha-2-macroglobulin (a2M) by proteinases in synovial fluids (SF) was indirectly measured by determining trypsin binding to solid-phase immunoadsorbed SF-a2M. In addition immune complexes (IC) were assessed by the solid-phase C1q-binding assay as well as the solid-phase conglutinin binding assay in rheumatoid (RA; n = 25) and osteoarthritic (OA; n = 9) SF. Elevated levels were found as follows: a2M X proteinase complexes (a2M X P) in 73.5% (RA, n = 20; OA, n = 5), solid-phase C1q-binding IC (C1q-IC) in 52% (13 out of 25 RA-SF) and bovine conglutinin binding IC (KgB-IC) in 54% (13 out of 24 RA-SF). All OA-SF were in either IC assay negative. Consumption of a2M in OA-SF and seronegative RA-SF was not more than 15% of total SF-a2M, showing a mean value of 19.5 and 13.5 micrograms a2M X P/ml SF. Seropositive RA-SF had an a2M X P mean value of 96.4 micrograms/ml SF, which differed significantly (p less than or equal to 0.05) from the former two groups. Similarly, RA-SF which were negative in either IC assay had a low a2M X P mean value (20.0 micrograms/ml SF). This contrasted sharply with the a2M X P means obtained in IC-positive RA-SF, which amounted to 131.5 micrograms a2M X P/ml SF in C1q-IC positive RA-SF and to 110.4 micrograms a2M X P/ml SF in KgB-IC positive RA-SF, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of C1q- and conglutinin-binding immune complexes with high consumption of alpha-2-macroglobulin in synovial fluids of patients with rheumatoid arthritis. 620 49

Pregnancy-associated plasma protein A (PAPP-A) has been obtained in an enriched state under mild conditions of purification involving cibacron blue dye-ligand chromatography, negative antibody-affinity chromatography and gel filtration. The product was a mixture of PAPP-A and alpha-2-macroglobulin (alpha 2M). The ability of these proteins to bind 125I-trypsin and 125I-plasmin was studied. In contrast to previous studies by others, there was no evidence that PAPP-A could bind either protease. It is pointed out that protease-inhibitory activity in samples of PAPP-A can be due to the presence of very small amounts of contaminating alpha 2M in the preparations of PAPP-A. In further experiments PAPP-A did not inhibit the complement-induced lysis of sensitized red cells. Finally, cyanogen bromide peptide mapping experiments failed to yield evidence of structural homologies between PAPP-A and alpha 2M.
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PMID:Pregnancy-associated plasma protein A: purification under mild conditions, peptide mapping and tests for possible interactions with trypsin, plasmin and complement. 620 4

Serum trypsin esterolytic activity was measured in 106 sera from 61 controls and 45 patients with pancreatitis. A trypsin specific synthetic substrate, N-alpha-benzoyl-L-arginine-paranitroanilide, was used. High levels of enzymatically active trypsin were shown to be present in serum of patients with pancreatitis. No difference between the two samples was noticed for the serum concentrations of alpha-1-antitrypsin and alpha-2-macroglobulin (the two main serum trypsin inhibitors). Active trypsin was contained in the high molecular weight fraction of plasma proteins, corresponding to a complex with alpha-2-macroglobulin. The determination of serum typsin activity as a sensitive test for detection of pancreatitis was demonstrated to be statistically significant.
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PMID:"Tryptic-like" activity in sera of patients with pancreatitis. 625 87

The capacity of malignant cells to invade and disseminate throughout the tissues is partly due to the fact that these cells synthesize and secrete proteases and plasminogen activators. Its growth can be inhibited by antiproteolytic substances in vitro or by natural inhibitors such as alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin (A2MG). It is a known fact that in cervical cancer, serum A1AT levels are elevated, but so far it has not been determined if serum proteolytic activity is elevated and if both occur simultaneously in vaginal fluid. 32 cases of invasive carcinoma of the cervix, and 25 non-cancerous women were studied. A1AT, A2MG, cathepsin B, trypsin inhibitory capacity (TIC), plasminogen and proteins in plasma and vaginal fluid were studied. In cancer cases, proteolytic activity of serum and vaginal fluid (cathepsin B) is elevated, when compared to controls (p less than 0.001). A1AT and A2MG levels are clearly elevated in plasma, but not in the vaginal fluid; TIC was elevated in serum in cancer cases (1.31 vs. 1.74 p less than 0.005) but was not altered in vaginal fluid. It was found that in cases of carcinoma in situ cathepsin B, plasminogen, A1At and A2MG and CIT were significantly increased (p less than 0.001, p less than 0.001, p less than 0.001 and p less than 0.01 respectively). In vaginal fluid the only statistically significant figure increased was cathepsin B (p less than 0.001). These studies show an altered protease-antiprotease balance in patients with carcinoma of the cervix uteri.
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PMID:Protease and antiprotease concentrations in serum and vaginal fluid of patients with carcinoma of the cervix. 701 Dec 40

alpha-Macroglobulin and murinoglobulin were purified to homogeneity from Syrian hamster plasma and their properties were compared with those of their respective homologs from other mammals. The trypsin-inhibiting capacity of hamster murinoglobulin was much weaker than those of rat and mouse murinoglobulins. Hamster alpha-macroglobulin was cleaved by trypsin at a number of sites whereas the human homolog was split essentially only in a "bait" region into two fragments of similar size. Hamster alpha-macroglobulin treated with methylamine differed from that treated with trypsin in the electrophoretic mobility, intensity of fluorescence induced by binding of bis(8-anilino-1-naphthalenesulfonate), and plasma clearance pattern, whereas virtually no difference was observed between the human homologs treated in the same manner. The reaction of hamster alpha-macroglobulin with methylamine, as measured by the generation of thiol groups and the decrease in trypsin-protein amidase activity, was much slower than that of the human homolog. Trypsin in a complex with hamster alpha-macroglobulin retained its fibrinolytic activity, but this was not the case for human or rabbit alpha-2-macroglobulin. These results suggest that, compared with the human homolog, hamster alpha-macroglobulin is more loosely packed in the native state, undergoes conformational change more slowly on treatment with methylamine, and less efficiently hinders the access of proteinaceous substrates to trapped proteinase. The serum concentration of hamster alpha-macroglobulin was 6.9 mg/ml, or about 3-fold higher than that of the human type, and showed little change during the acute-phase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hamster alpha-macroglobulin and murinoglobulin: comparison of chemical and biological properties with homologs from other mammals. 750 51

A crosslinked preparation of alpha-2-macroglobulin was obtained by treatment of the purified human plasma inhibitor with glutaraldehyde at low temperature. The preparation migrated as a 780 KDa polypeptide in SDS-PAGE and with mobility comparable with that of trypsinized native alpha-2-macroglobulin under nondenaturing conditions. Trypsinization of the glutaraldehyde treated alpha-2-macroglobulin further increased its electrophoretic mobility in non-denaturing gels and resulted in the association of the proteinase with the crosslinked inhibitor. Trypsin associated with crosslinked alpha-2-macroglobulin, unlike that associated with native inhibitor was incompletely protected from soybean trypsin inhibition.
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PMID:A crosslinked tetrameric alpha 2M that binds but incompletely entraps trypsin. 753 36

Gingival crevicular fluid (GCF) was collected from chronic periodontitis patients using plastic micropipettes and coverslip smears stained with antibodies for leukocyte markers and Toluidine Blue for mast cells. The smears consisted of 70-80% granulocytes, 10-20% monocytes/macrophages, 5% mast cells and 5% T lymphocytes; no B lymphocytes were found. Proteases and inhibitors in GCF cells were investigated by enzyme cytochemistry using 2-methoxy-4-naphthylamine-linked peptide substrates and simultaneous coupling to Fast Blue B and immunocytochemistry using biotinylated secondary antibodies and an alkaline phosphatase/new fuchsin detecting system. Elastase was detected in granulocytes, cathepsin B in macrophages, dipeptidyl peptidases II and IV in a small proportion of macrophages, dipeptidyl peptidase IV in a few T lymphocytes, tryptase in mast cells and alpha-1-proteinase inhibitor and alpha-2-macroglobulin in some macrophages. GCF was also collected on filter paper strips and eluted into buffer for biochemical enzyme assays. Lysis of cells by addition of detergent to the elution buffer increased activities to 140-240% of control values. Removal of cells by centrifugation reduced measured activities to 1-30% of original figures; this effect was less if samples were pre-treated with detergent. Proteases from inflammatory cells therefore appear to make up most of the measured enzyme activity in GCF, and this association may explain recent correlations with periodontal disease progression.
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PMID:Investigations into the cellular contribution to host tissue proteases and inhibitors in gingival crevicular fluid. 920 22

Chagas' disease is caused by the protozoan Trypanosoma cruzi. The acute phase of T. cruzi infection, which can be conveniently studied in mouse models, is thought to be a determinant of survival and of the pathological features of the chronic phase. With regard to the occurrence of early death and parasitaemia levels C3H and C57/B16 mice are classically classified as 'susceptible' and 'resistant' to T. cruzi infection, respectively. Alpha-2-macroglobulin (A2M) is a physiological proteinase inhibitor found in tissues and in the plasma of mammals. Previous studies showed that A2M plasma levels increase in C3H mice acutely infected by T. cruzi but do not change in C57/B16 mice. This difference might involve two possible phenomena, concerning A2M synthesis and/or clearance by its receptor (A2M-R). In this study, we examined by flow cytometry the binding of A2M-trypsin conjugated with FITC to macrophages from normal and T. cruzi-infected C3H and C57/B16 mice. Our present results show for the first time that A2M-R is expressed more (by approximately 33%) in the surface of cells from normal C57/B16 as compared to C3H mice. We also show that A2M-R expression is up-regulated in both strains during acute T. cruzi infection, but at higher levels and earlier in C57/B16 mice. At the same time, peritoneal cells become activated as judged by: (1) increase of their size and granularity; (2) gradual increase of Fc gamma RII/III expression assayed by 2.4G2 binding; (3) down-modulation of F4/80 binding, a mAb that recognizes an antigen typically expressed in resident macrophages. Finally, our results indicate that as macrophages become activated in vivo a higher expression of A2M-R is observed.
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PMID:Alpha-2-macroglobulin receptor is differently expressed in peritoneal macrophages from C3H and C57/B16 mice and up-regulated during Trypanosoma cruzi infection. 978 74

Data on study of action plasma inhibitors on activity of pancreatic proteolytic enzymes (trypsin, chymotrypsin) and plant proteinases (papain, bromelain), included in composition of enzyme mixes, used for orally application are submitted. It is established, that serine proteases are more sensitive to inactivation of plasma inhibitors, than cysteine enzymes. Main inhibitor of the papain and bromelain is alpha-2-macroglobulin in complex with which they preserve significant part of initial activity. A high-sensitivity method of determination of activity enzyme combinations, enabling to detect nanograms of them in presence of plasma inhibitors is offered. It can be used for study pharmacokinetic and optimization of enzyme mixes application in clinical practice.
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PMID:[Effect of blood plasma inhibitors on activity of serine and cysteine proteinases]. 1040 46


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