title: Pathobiochemistry of sepsis: role of proteinases, proteinase inhibitors and oxidizing agents.
abstract: Degradation of structural elements and excessive consumption of humoral factors, especially of plasma proteinase inhibitors, by proteolysis and/or oxidation is a major cause of multiple organ failure in sepsis or septic shock. Such pathobiochemical reactions seem to be induced primarily by extracellularly liberated lysosomal proteins from PMN granulocytes (e.g. elastase, cathepsin G, myeloperoxidase, lactoferrin) as well as oxygen radicals produced during extensive phagocytosis. In clinical studies on septicemia and septic shock the consumption of plasma proteins including proteinase inhibitors was inversely correlated to the liberation of lysosomal factors, especially the granulocytic elastase. Administration of relatively specific elastase-cathepsin G-inhibitors (Bowman-Birk inhibitor, eglin) in experimental septicemia proved to be a promising therapeutic approach to reduce consumption of plasma proteinase inhibitors and development of interstitial lung edema in severe inflammation.
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005176:Factor XIII / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000097:blood*; D011480:Protease Inhibitors / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000209:etiology; D012772:Shock, Septic / Q000097:blood
chemical_list: D001798:Blood Proteins; D011480:Protease Inhibitors; D000990:Antithrombin III; D005176:Factor XIII; D010447:Peptide Hydrolases