Subcellular localization and further characterization of a new elastase inhibitor from pneumococci.
Streptococcus pneumoniae contains an inhibitor of human neutrophil elastase. The agent does not inhibit other proteases, including neutrophil cathepsin G and pancreatic elastase. It is active in the presence of insoluble elastin as well as synthetic elastase substrates. The inhibitor is present in the pneumococcal cell membrane. [125I]elastase binding studies and inhibition experiments with intact bacterial autoplasts suggest that this agent has its elastase-binding site(s) exposed on the outside of the bacterial cell membrane. Native and randomized membrane vesicles also show equal inhibitory activity. Active inhibitor can be solubilized from pneumococcal membranes by treatment with a dipolar ionic detergent and can then be reconstituted, in active form, within artificial liposomes. Complex formation between the neutrophil elastase inhibitor and neutrophil elastase may involve noncovalent associations. Although elastase containing a covalently bound substrate analog no longer binds the pneumococcal inhibitor, the present study shows that complex formation is nevertheless independent of neutrophil elastase catalytic activity. Specific inhibitor activity and inhibitor release during bile salt-stimulated autolysis are greater in a nonnecrotizing pneumococcal strain (type I) than they are in a necrotizing strain (type III) or in Klebsiella pneumoniae. These results may help explain the frequent resolution of some pneumococcal pneumonias, despite the presence in the early pneumonic exudate of many neutrophils containing an elastolytic protease capable of injuring lung connective tissue.
D001329:Autolysis; D002462:Cell Membrane / Q000201:enzymology; D004549:Elastin / Q000378:metabolism; D006801:Humans; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D004549:Elastin; D010196:Pancreatic Elastase