The role of phagocyte proteinases and proteinase inhibitors in multiple organ failure.
Although numerous other inflammatory mediators are important, the following review of our research and that of other authors reveals a prominent role for the phagocyte proteinases, polymorphonuclear (PMN) elastase and cathepsin B, in the development of multiple organ failure. The release of these enzymes in relation to the severity of trauma- and/or infection-induced inflammation was clearly verified in a variety of clinical studies. The amounts of the extracellularly discharged phagocyte proteinases were highly predictive of forthcoming organ failure and ultimate patient outcome. Moreover, the consumption of important proteinase inhibitors (e.g., alpha 1-proteinase inhibitor, antithrombin III) and other plasma proteins (e.g., fibrinogen), which are highly susceptible to proteolytic degradation, coincided with the occurrence of proteolytic activity, especially that of PMN elastase. Therefore, the therapeutic use of specific PMN elastase and/or thrombin inhibitors should prevent multiple organ failure or at least reduce severe signs of inflammation.
Jochum
M
M
Abteilung für Klinische Chemie, Klinikum Innenstadt der Ludwig-Maximillians-Universität München, Germany.
Gippner-Steppert
C
C
Machleidt
W
W
Fritz
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002401:Cathepsin B / Q000097:blood / Q000502:physiology*; D056668:Cathepsin L; D002403:Cathepsins / Q000097:blood / Q000502:physiology; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D019272:Leukocyte Elastase; D009102:Multiple Organ Failure / Q000201:enzymology* / Q000503:physiopathology; D009104:Multiple Trauma / Q000097:blood / Q000503:physiopathology; D010196:Pancreatic Elastase / Q000097:blood / Q000502:physiology*; D010586:Phagocytes / Q000201:enzymology*; D010587:Phagocytosis; D011379:Prognosis; D011480:Protease Inhibitors / Q000097:blood*
D018836:Inflammation Mediators; D011480:Protease Inhibitors; D002403:Cathepsins; D010450:Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L