Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peritoneal cavity of guinea pigs proved to be a rich source of mononuclear cells (34-52%) with fibrinogen or fibrin (Fib) on their surface. The Fib was readily detected on the surface of viable cells in suspension by fluorescence microscopy using antisera to guinea pig fibrinogen. The fluorescent staining occurred either in a speckled distribution, similar to that of cytophilic IgG, or in a distinctive net-like pattern that probably represented fibrin formation on the cell surface. The binding of Fib to the cell surface required calcium, but not magnesium, in the medium and could occur in vitro during incubation in heparinized plasma that contained fibrinogen concentrations comparable to that in normal peritoneal fluid (0.58 mg/ml). Cell surface Fib was more susceptible to plasmin and trypsin digestion than surface cytophilic IgG. By morphologic and physiologic criteria, cells exhibiting surface Fib were chiefly, if not exclusively, macrophages. Granulocytes, erythrocytes, and lymphocytes from lymph node and thymus had no sppreciable Fib. Cells with surface Fib were rarely observed among mononuclear cells prepared by Ficoll-Hypaque sedimentation of guinea pig and human blood (1.4 and 4.6%, respectively). Pulmonary alveolar macrophages, functionally distinct from peritoneal macrophages, lacked surface Fib (0.8%). Polymerization of Fib on the surface of macrophages might participate in certain cell interactions, such as the adherence of peritoneal macrophages during the antigen-induced macrophage disappearance reactions. The unexpected finding of Fib binding to the surfaces of peritoneal macrophages raises the possibility of a biologically significant interaction between these cells and the clotting system.
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PMID:Fibrinogen/fibrin on the surface of macrophages: detection, distribution, binding requirements, and possible role in macrophage adherence phenomena. 110 45

The production of interleukin (IL 1) by normal human peripheral blood monocytes purified by Ficoll-Hypaque density sedimentation, Percoll-gradient sedimentation, and plastic adherence can be detected as early as 30 min intracellularly, and extracellularly within 1 hr after stimulation with lipopolysaccharide (LPS). Production of mRNA coding for the isoelectric point 7.0 species of IL 1 was also detected as early as 1 hr after LPS stimulation and reached a maximum level at 6 hr. Cell-associated IL 1 activity could be extracted with CHAPS detergent from every cell fraction (i.e., membranes, cytosol, and particulates), but was present mainly (greater than 95%) in the cytosol of LPS-activated monocytes and the myelomonocytic cell line, THP-1. The apparent m.w. of IL 1 activity on high pressure liquid chromatography gel filtration in every cell fraction was approximately 23,000 daltons, with a minor peak at 31,000 daltons, whereas the IL 1 activity in the culture supernatants was 17,000 daltons. Western blotting analysis of LPS-stimulated monocyte extracts showed two forms of IL 1 corresponding to 31,000 daltons and 25,000 daltons. Exposure of viable cells to trypsin and plasmin released biologically active 23,000 dalton IL 1 only from IL 1-producing cells such as activated monocytes and IL 1-producing Ebstein-Barr virus B lymphocyte cell lines. Consequently, biologically active IL 1 is presumably exposed on the outer surface of cell membranes. Furthermore, IL 1 release by human monocytes in plasminogen-depleted fetal calf serum was considerably decreased. Conversely, supplementation of plasminogen-depleted serum with purified plasminogen restored the IL 1 production, suggesting that plasmin or plasmin-like factors may be involved in the regulation of the release of IL 1 from IL 1-producing cells. In conclusion, the results suggest that IL 1 is rapidly produced, is pooled in the cytosol, and in part is processed by enzymes, is transferred to the plasma membranes, and is then released from the cells. Tissue plasminogen activator and serum enzymes such as plasmin may therefore be involved in the release of IL 1 from IL 1-producing cells.
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PMID:Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin. 242 Aug 74

Discrepancies in correlations between fibrinolytic activity and metastatic potential of malignant cells has resulted in speculation on the putative role of plasminogen activators (PA) in cancer. In this report we have compared lymphocyte PA from 40 patients with chronic lymphocytic leukemia (CLL) to normal human B- and T-lymphocytes. Lymphocytes were isolated from peripheral blood by Ficoll-Hypaque centrifugation. The B- and T-cells were further separated on nylon wool columns. Cell PA activity and cell membrane PA were determined using 3H-fibrin-coated plates with added human plasminogen. Lymphocytes did not lyse 3H-fibrin in the absence of plasminogen. Plasminogen-dependent fibrinolytic activities of normal B- and T-lymphocytes were comparable. The addition of protease inhibitors with trypsin or plasmin specificity to lymphocytes significantly inhibited normal PA, thus substantiating the serine protease spectrum of lymphocyte PA. Examination of lymphocytes from greater than 95% of patients with chronic lymphocytic leukemia revealed a marked decrease in lymphocyte and cell membrane PA as compared to normals. No correlation between Stage of CLL and lymphocyte PA was observed. Likewise, an inhibitor of PA in CLL lymphocytes was not detected. The function of PA in normal B-lymphocyte physiology and the potential pathogenetic role of diminished PA in CLL lymphocytes remain to be explored.
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PMID:Plasminogen-dependent fibrinolytic activity in normal human lymphocytes: diminished lymphocyte plasminogen activator in chronic lymphocytic leukemia. 392 13