Cefoperazone prevents the inactivation of alpha(1)-antitrypsin by activated neutrophils.
At sites of neutrophilic inflammation, tissue injury by neutrophil elastase is favored by phagocyte-induced hypochlorous acid-dependent inactivation of the natural elastase inhibitor alpha(1)-antitrypsin. In the present study, cefoperazone prevented alpha(1)-antitrypsin inactivation by neutrophils and reduced the recovery of hypochlorous acid from these cells. Moreover, the antibiotic reduced the free elastase activity in a neutrophil suspension supplemented with alpha(1)-antitrypsin without affecting the cells' ability to release elastase. These data suggest that the drug inactivates hypochlorous acid before its reaction with alpha(1)-antitrypsin, thereby permitting the antiprotease-mediated blockade of released elastase. In conclusion, cefoperazone appears to have the potential for limiting elastase-antielastase imbalances, attenuating the related tissue injury at sites of inflammation.
Dallegri
F
F
Department of Internal Medicine, University of Genoa Medical School, Genoa, Italy.
Dapino
P
P
Arduino
N
N
Bertolotto
M
M
Ottonello
L
L
D002438:Cefoperazone / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000187:drug effects / Q000378:metabolism*
D002511:Cephalosporins; D000515:alpha 1-Antitrypsin; D006997:Hypochlorous Acid; D002438:Cefoperazone; D010196:Pancreatic Elastase