Neutrophil-mediated injury to gastric mucosal surface cells

Abstract

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.

Plaunotol Prevents the Progression of Acute Gastric Mucosal Lesions Induced by Compound 48/80, a Mast Cell Degranulator, in Rats

“…Accordingly, there may be a possibility that postadministered plaunotol attenuates increased lipid peroxidation in the gastric mucosal tissue of C48/80-treated rats through inhibition of lipid peroxidation mediated by activated neutrophils in the gastric mucosal tissue. In addition, it has been shown in an in vitro experiment that neutrophil-mediated injury to gastric mucosal surface cells involves superoxide radical and hypochlorous acid but not neutral trypsin-like proteinase or hydroxyl radical [40] . Therefore, these fi ndings suggest that plaunotol could exert a preventive effect on the progression of C48/80-induced acute gastric mucosal lesions in rats by attenuating enhanced increases in neutrophil infi ltration and lipid peroxidation in the gastric mucosal tissue possibly through its inhibitory action on the expression of adhesion molecules CD11b and CD18 and the formation of superoxide radical in infi ltrated neutrophils in addition to its direct antioxidant actions to scavenge superoxide radical and to inhibit lipid peroxidation.…”

The effect of proton pump inhibitors on the gastric mucosal microenvironment

“…Infiltrating neutrophils play an important role in gastric mucosal injury, particularly in regard to oxidative stress and inflammatory cytokines. 6 Gastric mucosa neutrophils also defend against foreign bacterial infection. The effect of PPIs on gastric mucosa neutrophil-related oxidative stress and the innate immunity of neutrophils in the gastric mucosa need further investigation, particularly considering the heterogeneity of human hosts.…”

“…5 With their destructive potential, neutrophils enter peripheral tissue and interact closely with host cells. 5,6 Helicobacter pylori (H. pylori) infection is a global threat and commonly persists for life unless treated. H. pylori is one of the major factors related to the pathogenesis of gastric mucosa injury and the main cause of chronic gastritis, gastric mucosal atrophy, peptic ulcer and some forms of gastric cancer.…”

Allium Cepa Ameliorates Ethanol-Induced Gastric Injury in Rats Via Reduction in Gastric Neutrophils Infiltration

“…Injury produced by neutrophils occurs as a result of their capacity to produce Reactive Oxygen Species (ROS), (Wallace et al, 1992). Study by Kozol et al, (1994) implicated superoxide in neutrophil-mediated gastric injury. This present study demonstrates that Allium cepa increased gastric antioxidant activities, which is important in the body's defense system (Dhanprakash and Garima, 2007;Hwan et al, 2011), as earlier reported (Ige et al, 2011;Ige et al, 2012b).…”