NEUTROPHIL-MEDIATED INJURY TO GASTRIC-MUCOSAL SURFACE CELLS

Neutrophils (PMNs) have been implicated in the pathogenesis of gastrit is. This study evaluates the magnitude and mode of PMN-mediated damage to gastric mucosal surface cells (GSC) in a system independent of vas cular and neural factors. Rabbit GSC were freshly isolated and preload ed with Cr-51. GSC were then incubated for 1 hr or 4 hr with freshly i solated human PMNs at varying effector-to-target cell ratios. Injury t o GSC was assessed as percent specific Cr-51 released and by electron microscopy. We found minimal GSC injury using nonactivated PMNs. Incub ation with PMNs activated with formyl-methionyl-leucyl-phenalalanine ( FMLP), however, resulted in significant GSC injury at the 20:1 PMN/GSC ratio, 33.2 +/- 1.8% Cr-51 release (P < 0.001 compared to nonactivate d PMNs). Electron microscopy revealed well-preserved gastric surface c ells after exposure to nonstimulated PMNs. GSC exposed to activated PM Ns (20:1 PMN/GSC ratio) were severely injured. Proteinase inhibitors a nd dimethylsulfoxide failed to diminish PMN-mediated GSC injury. Conve rsely, superoxide dismutase (SOD) inhibited GSC injury by more than 50 % IP < 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 hypoch lorous acid and not neutral trypsinlike proteinases or hydroxyl radica ls.