Polymorphonuclear leukocytes-induced injury in hypoxic cardiac myocytes.
Growing evidence suggests that free radicals derived from polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia-reperfusion injury. To elucidate the cellular mechanism by which activated PMNs exacerbate ischemic myocardial damage, we investigated the extent of cell injury, assessed by the morphological deterioration, free radical generation, and lipid peroxidation in mouse embryo myocardial cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. When myocardial cell sheets were subjected to hypoxia and glucose-free media, myocardial cells were injured (cristalysis in the mitochondria and disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emission and production of thiobarbituric acid-reactive substances in the coincubated cells increased markedly compared with myocardial cells or PMNs alone. The augmented lipid peroxidation coincided with the progression of myocardial cell injury. Catalase inhibited the myocardial cell injury by 52%, the chemiluminescence by 46%, and lipid peroxidation by 50%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correlates with membrane damage and contributes to the propagation of irreversible myocardial cell damage.
Kuzuya
T
T
Department of Pathophysiology, Osaka University School of Medicine, Japan.
Fuji
H
H
Hoshida
S
S
Nishida
M
M
Goshima
K
K
Hori
M
M
Kamada
T
T
Tada
M
M
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D015687:Cell Hypoxia; D005609:Free Radicals / Q000032:analysis*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D051379:Mice; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013858:Thiobarbiturates / Q000032:analysis; D015054:Zymosan / Q000494:pharmacology
D005609:Free Radicals; D013858:Thiobarbiturates; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D002374:Catalase; D013482:Superoxide Dismutase; C029684:thiobarbituric acid; D013755:Tetradecanoylphorbol Acetate