1993 Fiscal Year Final Research Report Summary
LUNG FIBROBLAST GROWTH-STIMULATIONG ACTIVITY OF SERINE PROTEASES AND ITS PATHOLOLOGICAL SIGNIFICANCE
| Project/Area Number |
04670468
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | SCHOOL OF MEDICAL SCIENCES, THE UNIVERSITY OF TOKUSHIMA |
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Principal Investigator |
YASUOKA Susumu SCHOOL OF MEDICAL SCIENCES, THE UNIVERSITY OF TOKUSHIMA, PROFESSOR, 医療技術短期大学部, 教授 (30035414)
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| Co-Investigator(Kenkyū-buntansha) |
UETA Yuji 3RD DEPATMENT OF INTERNAL MEDICINE SCHOOL OF MEDICINE, THE UNIVERSITY OF TOKUSHI, 医学部, 助手 (30243679)
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| Project Period (FY) |
1992 – 1993
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| Keywords | serine protease / fibroblast / pulmonary fibrosis / bleomycin / plasmin / trypsin / thrombin / sputum |
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| Research Abstract |
THIS STUDY WAS PERFORMED TO CLARIFY ROLE OF PROTEASES, ESPECIALLY SERINE PROTEASES IN PATHOGENESIS OF PULOMONARY FIBROSIS.(1) EFFECTS OF SERINE PROTEASES ON LUNG FIBROBLAST IN VITRO- WE COMPARED LUNG FIBROBLAT GROWTH-STIMULATING ACTIVITY (FGA) OF MAIN SERINE PUROTEASES IN VITRO, AND EXAMINED THE MECHANISM OF FGA.THE ACTIVITIES OF THE ENZYMES WERE MEASURED BY SPECTROFLUOROMETRIC METHOD WITH SYNTHETIC PEPETIDES FOR EACH ENZYME, AND THESE ENZYMES WERE ADDED TO THE ASSAY SYSTEM OF FGA AT CONCENTRATION OF 7-10^0-7X10^5 UNIT/ML.HUMAN THROMBIN AND PLASMIN, AND BOVINE TRYPSIN AND CHYMOTRYPSIN SHOWED CLEAR FGA, BUT PORCINE PANCREATIC ELASTASE AND HUMAN NEUTROPHIL ELASTASE DID NOT SHOW ANY FGA.A SPECIFIC LOW-MOLECULAR WIGHT THROMBIN INHIBITOR, ARGATROBA(MW 562), INHIBITED NOT ONLY THE ENZYME(PEPTIDOLYTIC) ACTICIVITY OF THROMBIN, BUT ALSO ITS FGA AT THE SAME CONCENTRATION.THESE RESULTS SUGGEST THE SERINE PROTEASES CAN BE CLASSIFIED INTO AT LEAST TWO GROUPS, SHOWING FGA AND CYTOTOXIC ACTICITY, RESPECTIVELY, AND THAT THE FGA OF THE FORMER GROUP IS MEDIATED BY THEIR CATALYTIC(ENZYMATIC) ACTION.(2) CHANGES OF ACTIVITIES OF SERINE PUROTEASES IN RAT LUNG TISSUE OF BLEOMYCIN.(BLM)-INDUCED PULMONARY FIBROSIS-INCREASE OF FIBROBLASTS IN THE LUNG TISSUE WERE THE MOST MARKED AT 4-7 DAYS AFTER SINGLE ADMINISTRATION OF BLM VIA TRACHEA.THE ACTIVITES OF PLASMIN, THROMBIN AND TRYPSIN IN THE LUNG TISSUES SHOWED PROPINANT INCREASE, PLASMIN ACTIVITY SHOWING MOST MARKED INCREASE, AT 7 DAYS AFTER THE ADMINISTRATION.BUT ACTIVITIES OF ELASTASE, CHYMOTRYPSIN, UROKINASE AND FACTOR X SHOWED NO SIGNIFICANT INCREASE IN THE LUNG TISSUES.THESE RESULTS SUGGEST THAT PLASMIN IS MOST INTIMATELY RELATED TO THE BLM-INDUCED PULMONARY FIBROSIS, OF THE SERINE PROTEASES.(3) WE FOUND OUT NEW TRYPTASE IN HUMAN BRONCHAIL SECRETIONS, AND PURIFIED THIS ENZYME TO SINGLE BAND ON PAGE FROM MUCOID SPUTA OF PATIENTS CHRONIC AIRWAY DISEASES.THIS TRYPTASE SHOWED FGA ALSO.WE EXAMINED PROTEASE INHIBITORS IN BRONCHIA
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