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DOI: 10.1055/s-0038-1661188
Plasminogen Activator and Plasminogen Activator Inhibitor Associated with Granulomatous Inflammation: A Study with Murine Leprosy
Publication History
Received 02 December 1983
Accepted 08 August 1984
Publication Date:
19 July 2018 (online)
Summary
Plasminogen activator that is associated with the development of hypersensitivity granulomas (gPA) was partially purified from a saline soluble fraction of murine lepromas elicited in “resistant” mice, C57BL/6N. The gPA was shown to consist of two subspecies (23,000 and 48,000 in molecular weight) with essentially identical enzymologic properties. The gPA was found to be a relatively heat stable weakly alkaline serine proteinase with trypsin-like characteristics in the specificity for synthetic substrates and proteinase inhibitors. It showed a high affinity for H- D-Ile-Pro-Arg-pNA (Km = 1.4 × 10-4 M) H-D-Val-Leu-Lys- pNA (Km = 5.2 × 10-4 M), and L-pyroGlu-Gly-Arg-pNA (Km = 9.3 × 10-4 M). The gPA did not demonstrate antigenic cross reaction with urokinase-type or tissue-type plasminogen activator.
Two distinct enzymatic regulators of the gPA were also demonstrated in the saline soluble fraction of the hypersensitivity granulomas. The gPA and its regulation are assumed to be correlated with macrophage activation in the hypersensitivity granulomas
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References
- 1 Epstein WL, Krasnobrod H. The origin of epithelioid cells in experimental granulomas of man. Lab Invest 1968; 18: 190-195
- 2 Black M, Epstein WL. Formation of multinucleate giant cells in organized epithelioid cell granulomas. Am J Pathol 1974; 74: 263-274
- 3 Hsu WY, Hsu HF, Lust GL, Davis JR. Organized epithelioid cell granulomata elicited by schistosome eggs in experiemental animals. J Reticuloendothel Soc 1972; 12: 418-435
- 4 von Lichtenberg F, Erickson DG, Sadun EH. Comparative histopathology of schistosome granulomas in the hamster. Am J Pathol 1973; 72: 149-168
- 5 Epstein WL, Fukuyama K, Danno K, Kwan-Wong E. Granulomatous inflammation in normal and athymic mice infected with Schistosoma mansoni: an ultrastructural study. J Pathol 1979; 127: 207-215
- 6 Williams WJ, Erasmus DA, Jenkins D, Valerie-James EM, Davies T. A comparative study of the ultrastructure and histochemistry of sarcoid and tuberculous granulomas. In: Fifth International Conference on Sarcoidosis. Leninsky L, Macholda F. (Eds) Universita Karlova; Praha: 1971. pp 115-120
- 7 Closs O, Haugen OA. Experimental murine leprosy 4. The gross appearance and microscopic features of the local infiltrate after subcutaneous inoculation of C3H and C57/BL mice with Mycobacterium lepraemurium. Acta Pathol Microbiol Scand [A] 1975; 83: 59-68
- 8 Izaki S, Goldstein SM, Fukuyama K, Epstein WL. Fibrin deposition and clearance in chronic granulomatous inflammation: Correlation with T-cell function and proteinase inhibitor activity in tissue. J Invest Dermatol 1979; 73: 561-565
- 9 Izaki S, Isozaki Y, Satoh M, Hibino T, Kon S, Izaki M. Comparative study with two polar types of murine leprosy: An involvement of plasminogen activator and its possible regulating factor in the granulomatous tissue reaction. J Invest Dermatol 1983; 80: 81-85
- 10 Satoh M, Izaki S, Kon S, Izaki M. Fibrin deposition and fibroblasts proliferation in granuloma of murine leprosy. Comparison of two mouse strains with different immune reactions Experientia 1983; 39: 899-902
- 11 Kawaguchi Y, Matsuoka M. Observation of host reactions to murine leprosy bacilli in spread subcutaneous tissue preparations of various strains of mice. Jpn J Exp Med 1977; 47: 71-79
- 12 Haugen OA, Skjorten F, Closs O. Experimental murine leprosy 8. Ultrastructural features of inflammatory exudate and bacterial morphology in C3H and C57BL mice after footpad inoculation with Mycobacterium lepraemurium. Acta Pathol Microbiol Scand [A] 1975; 83: 693-703
- 13 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275
- 14 Okamoto U, Nagamatsu Y, Tsuda Y, Okada Y. A new polypeptide substrate Suc-Tyr-Leu-Val-pNA, specific for spleen fibrinolytic proteinase (SFP). Biochem Biophys Res Commun 1980; 97: 28-32
- 15 Hibino T, Izaki S, Izaki M. Detection of serine proteinase inhibitors in human comified cells. Biochem Biophys Res Commun 1981; 101: 948-955
- 16 Segel IH. Enzyme kinetics: behaviour and analysis of rapid equilibrium and steady state enzyme systems. A Wiley-Interscience Publication; New York: 1975. pp 46-51
- 17 Unkeless JC, Tobia A, Ossowski L, Quigley JP, Rifkin DB, Reich E. An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. I. Chick embryo fibroblast cultures transformed by avian RNA tumor viruses. J Exp Med 1973; 137: 85-111
- 18 Deutsch DG, Mertz ET. Plasminogen; purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
- 19 Chase Jr T, Shaw E. Titration of trypsin, plasmin and thrombin with p-nitrophenyl-p’-guanidinobenzoate HC1. In: Methods in Enzymology 19. Perlman GE, Lorand L. (Eds) Academic Press; New York: 1970. pp 20-27
- 20 Laskowski M. Trypsinogen and trypsin. In: Methods in Enzymology 2. Colowick SP, Kaplan NO. (Eds) Academic Press; New York: 1955. pp 26-36
- 21 Unkeless JC, Gordon S, Reich E. Secretion of plasminogen activator by stimulated macrophages. J Exp Med 1974; 139: 834-850
- 22 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685
- 23 Heussen C, Dowdle EB. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulphate and copolymerized substrates. Anal Biochem 1980; 102: 196-202
- 24 Sumi H, Robbins KC. A functionally active heavy chain derived from human high molecular weight urokinase. J Biol Chem 1983; 258: 8014-8019
- 25 Holmberg L, Bladh B, Åstedt B. Purification of urokinase by affinity chromatography. Biochim Biophys Acta 1976; 445: 215-222
- 26 Rijken DC, Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 1981; 256: 7035-7041
- 27 Burnette WN. »Western blotting«: electrophoretic transfer of proteins from sodium dodecyl sulfate polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 1981; 112: 195-203
- 28 Hsu S-M, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J Histochem Cytochem 1981; 29: 577-580
- 29 Friberger P. Chromogenic peptide substrates: their use for the assay of factors in the fibrinolytic and the plasma kallikrein-kinin systems. Scand J Clin Lab Invest 1982; 42 Suppl (Suppl. 162) 9-98
- 30 Chapman Jr HA, Vavrin Z, Hibbs Jr JB. Macrophage fibrinolytic activity: identification of two pathways of plasmin formation by intact cells and of a plasminogen activator inhibitor. Cell 1982; 28: 653-662
- 31 Gordon S, Cohn Z. Bacille Calmette-Guerin infection in the mouse. Regulation of macrophage plasminogen activator by T-lymphocytes and specific antigen J Exp Med 1978; 147: 1175-1187
- 32 Issernoff RR, Fusenig NE, Rifkin DB. Plasminogen activator in differentiating mouse keratinocytes. J Invest Dermatol 1983; 80: 217-222
- 33 Bykowska K, Levin EG, Rijken DC, Loskutoff DJ, Collen D. Characterization of a plasminogen activator secreted by cultured bovine aortic endothelial cells. Biochim Biophys Acta 1982; 703: 113-115
- 34 Matsuo O, Rijken DC, Collen D. Comparison of the relative fibrinogenolytic, fibrinolytic and thrombolytic properties of tissue plasminogen activator and urokinase in vitro. Throm Haemostas 1981; 45: 225-229
- 35 Christman JK, Silverstein SC, Acs G. Plasminogen activators. In: Proteinases in Mammalian Cells and Tissues. Barrett AJ. (Ed) North- Holland Pub Comp; Amsterdam: 1977. pp 91-149
- 36 Moroi M, Aoki N. Isolation and characterization of alpha2-plasmin inhibitor from human plasma. A novel proteinase inhibitor which inhibits activator-induced clot lysis J Biol Chem 1976; 251: 5956-5965
- 37 Izaki S, Goldstein SM, Fukuyama K, Epstein WL. Tissue induction of a urokinase inhibitor associated with chronic granulomatous inflammation: Correlation with local fibrin deposition and clearing (in Japanese with English abstract). Blood and Vessel 1980; 11: 675-678
- 38 Goldstein SM, Izaki S, Epstein WL. Inhibition of plasminogen activator associated with chronic granulomatous inflammation. Thromb Res 1979; 16: 727-735
- 39 Izaki S, Fukuyama K, Epstein WL. Modulation of antithrombin and anti-fibrinolytic activities in tissue during the development of granulomas induced by Schistosoma mansoni. J Reticuloendothel Soc 1979; 26: 507-514