Relative role of chloramines, hypochlorous acid, and proteases in the activation of human polymorphonuclear leukocyte collagenase.
The activation of collagenase released by polymorphonuclear leukocytes (PMNs) has been extensively studied in vitro, but the activation of the enzyme in vivo is not fully understood. For further evaluation of the relative role of oxidative and proteolytic mechanisms in the activation of collagenase, PMNs were stimulated by serum-opsonized zymosan under both aerobic and anaerobic conditions. The results showed that similar amounts of collagenase were released by the PMNs under aerobic and anaerobic conditions, but the activity of the released collagenase was twice as high under aerobic conditions as under anaerobic conditions. Under aerobic conditions the enzyme was rapidly activated by hypochlorous acid and chloramines, which are products of the myeloperoxidase-H2O2-chloride system of the PMNs. There was also a slow proteolytic activation of the enzyme, which could be ascribed to cathepsin G and possibly to some other serine proteases of PMNs. When extrapolating these findings to in vivo conditions, it seems probable that the oxidative activation of collagenase will proceed mainly by chloramines, which are more long-lived in the tissue than hypochlorous acid. In poorly oxygenated tissues, collagenase may be mainly activated by proteolytic mechanisms.
Claesson
R
R
Department of Oral Biology, Umeå University, Sweden.
Karlsson
M
M
Zhang
Y
Y
Carlsson
J
J
D000328:Adult; D000332:Aerobiosis; D000693:Anaerobiosis; D002478:Cells, Cultured; D002700:Chloramines / Q000494:pharmacology*; D017364:Collagenases / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000201:enzymology; D010450:Endopeptidases / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016897:Respiratory Burst / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D002700:Chloramines; D015842:Serine Proteinase Inhibitors; D006997:Hypochlorous Acid; D015054:Zymosan; D010450:Endopeptidases; D017364:Collagenases