Microbicidal mechanisms of human granulocytes: synergistic effects of granulocyte elastase and myeloperoxidase or chymotrypsin-like cationic protein.
The antibacterial activity of a myeloperoxidase (MPO)-glucose oxidase system was found to be greatly increased by granulocyte elastase, present in azurophil granules of human neutrophils. The MPO-H2O3-mediated killing of both Escherichia coli and Staphylococcus aureus was potentiated by granuocyte elastase at an acid pH, whereas at pH 7.4 only killing of E. coli was potentiated. The potentiating effect of elastase was not dependent on the enzymatic properties of the protein since it was not abolished by heating, which destroys the enzymatic activity. A peptide chloromethyl ketone elastase inhibitor abolished both elastolytic activity and the pctentiating effects on MPO-H2-O2-mediated bacterial killing. The antibacterial activity of chymotrypsin-like cationic protein of human neutrophils was also potentiated by elastase. Other degradative enzymes isolated from human granulocytes, e.g., collagenase and lysozyme, did not potentiate MPO-H2O2-mediated or cationic protein-dependent bacterial killing. The present study indicates that a neutrophil constitutent, elastase, which is not microbicidal by itself, can initiate sublethal changes that render some microorganisms more susceptible to the action of microbicidal agents like MPO and chymotrypsin-like cationic protein.
D001665:Binding Sites; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism*; D002918:Chymotrypsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004926:Escherichia coli / Q000378:metabolism; D005949:Glucose Oxidase / Q000494:pharmacology; D006098:Granulocytes / Q000382:microbiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000382:microbiology*; D003012:Microbial Collagenase / Q000494:pharmacology; D009113:Muramidase / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009195:Peroxidase / Q000494:pharmacology*; D010544:Peroxidases / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000378:metabolism
D001798:Blood Proteins; D005949:Glucose Oxidase; D010544:Peroxidases; D009195:Peroxidase; D009113:Muramidase; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D003012:Microbial Collagenase