Granulocyte proteinases as mediators of unspecific proteolysis in inflammation: a review.
In severe inflammatory response, various blood and tissue cells, including polymorphonuclear granulocytes, release lysosomal proteinases, extracellularly and into the circulation. Such enzymes, as well as normally intracellular oxidizing agents produced during phagocytosis, enhance the inflammatory response by degrading connective tissue structures, membrane constituents and soluble proteins by proteolysis or oxidation. We first used polymorphonuclear elastase (E) as a marker of such release reactions. The liberated proteinase competes with susceptible substrates, including alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin, and is eliminated finally as inactive enzyme-inhibitor complexes by the reticulo-endothelial system. Using an enzyme-linked immunosorbent assay, we determined the plasma levels of E-alpha 1PI following major abdominal surgery, multiple trauma and pancreatogenic shock. Whereas the operative trauma was followed by up to 3-fold increase of the E-alpha 1-PI, postoperative septicemia was associated with a 10 to 20 fold increase. The increase of E-alpha 1-PI and a concomitant decrease of plasma factors, such as antithrombin III, clotting factor XIII and alpha 2-macroglobulin, were correlated. Multiple trauma causes a substantial increase of E-alpha 1-PI up to 14 hours after accident. The released elastase seems to correlate with severity of injury, but assessing the relationship to consumption of plasma factors is complicated by concomitant transfusions. In acute pancreatitis, peaks, of E-alpha 1-PI coincide with a massive consumption of antithrombin III and alpha 2-macroglobulin during shock.
D001798:Blood Proteins; D006098:Granulocytes / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D010196:Pancreatic Elastase / Q000097:blood; D010195:Pancreatitis / Q000201:enzymology; D010447:Peptide Hydrolases / Q000097:blood*; D011480:Protease Inhibitors / Q000097:blood; D018805:Sepsis / Q000201:enzymology; D014947:Wounds and Injuries / Q000201:enzymology; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D010447:Peptide Hydrolases; D010196:Pancreatic Elastase