Hemorrhagic activity and muscle damaging effect of Pseudomonas aeruginosa metalloproteinase (elastase).
Pseudomonas aeruginosa elastase, a Bacillus subtilis thermolysin-like zinc-proteinase was examined for hemorrhagic activity and its effect on muscle and endothelial cells. Subcutaneous and intramuscular injections of elastase into mice caused severe hemorrhage with an acute increase of creatine phosphokinase activity in serum. The elastase also possessed fibrinogenolytic and fibrinolytic activities. The Aalpha and Bbeta chains of fibrinogen were completely hydrolyzed as demonstrated by their electrophoretic disappearance on SDS polyacrylamide gels. The pathological study indicates that elastase induces changes in the structure of the vascular wall and causes leakage of the plasma component and red and white blood cells into the extravascular tissue. This is further supported by results showing injury to cultured endothelial cells and macrophages. These data indicate that P. aeruginosa elastase directly affects endothelial cells and destroys the basement membrane of blood vessels to cause hemorrhage. Since fibrinogenolytic activity is an additional component of this elastase and this activity induces the hemorrhagic tendency, the damage in tissues could become increasingly severe.
Komori
Y
Y
Department of Microbiology, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, 468-8503, Nagoya, Japan. ykomori@meijo-u.ac.jp
Nonogaki
T
T
Nikai
T
T
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D010450:Endopeptidases / Q000737:chemistry; D004730:Endothelium, Vascular / Q000473:pathology; D005340:Fibrinogen / Q000737:chemistry / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006470:Hemorrhage / Q000139:chemically induced*; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D010196:Pancreatic Elastase / Q000633:toxicity*; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000254:growth & development
D005343:Fibrinolytic Agents; D005340:Fibrinogen; D003402:Creatine Kinase; D010450:Endopeptidases; D010196:Pancreatic Elastase