Neutrophil-mediated injury to gastric mucosal surface cells.
Neutrophils (PMNs) have been implicated in the pathogenesis of gastritis. This study evaluates the magnitude and mode of PMN-mediated damage to gastric mucosal surface cells (GSC) in a system independent of vascular and neural factors. Rabbit GSC were freshly isolated and preloaded with 51Cr. GSC were then incubated for 1 hr or 4 hr with freshly isolated human PMNs at varying effector-to-target cell ratios. Injury to GSC was assessed as percent specific 51Cr released and by electron microscopy. We found minimal GSC injury using nonactivated PMNs. Incubation with PMNs activated with formylmethionyl-leucyl-phenylalanine (FMLP), however, resulted in significant GSC injury at the 20:1 PMN/GSC ratio, 33.2 +/- 1.8% 51Cr release (P < 0.001 compared to nonactivated PMNs). Electron microscopy revealed well-preserved gastric surface cells after exposure to nonstimulated PMNs. GSC exposed to activated PMNs (20:1 PMN/GSC ratio) were severely injured. Proteinase inhibitors and dimethylsulfoxide failed to diminish PMN-mediated GSC injury. Conversely, superoxide dismutase (SOD) inhibited GSC injury by more than 50% (P < 0.001). In addition, glutathione peroxidase inhibited injury by 84% (P < 0.001). These data suggest that neutrophil-mediated injury to gastric surface cells in vitro involves superoxide anion and hypochlorous acid and not neutral trypsinlike proteinases or hydroxyl radicals.
Kozol
R
R
Department of Surgery, Veterans Administration, Allen Park, Michigan 48101.
Kopatsis
A
A
Fligiel
S E
SE
Czanko
R
R
Callewaert
D
D
D000818:Animals; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D003602:Cytotoxicity, Immunologic; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology*; D005756:Gastritis / Q000209:etiology; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008854:Microscopy, Electron; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D002860:Chromium Radioisotopes; D017382:Reactive Oxygen Species; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase