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Activated Neutrophils Impair Gastric Cytoprotection: Role of Neutrophil Elastase

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Abstract

Neutrophil elastase decreases production of PGI2 by cultured endothelial cells. Thus, neutrophil elastase may play an important role in gastric mucosal injury by decreasing the tissue level of PGI2, an important gastric cytoprotective substance. We examined whether activated neutrophils inhibit gastric PGI2 production in rats subjected to water-immersion restraint stress. Gastric 6-keto-PGF1α levels were determined by enzyme immunoassay. Gastric mucosal blood flow was determined by laser–Doppler flowmeter. Gastric microvascular permeability was determined by Evans blue leakage. Gastric levels of 6-keto-PGF1α were transiently increased 0.5 hr after the stress, followed by a decrease to below baseline at 6 hr, when mucosal blood flow fell to 60% of baseline. Gastric levels of 6-keto-PGF1α were significantly higher in animals with nitrogen mustard-induced leukocytopenia than in controls 1 and 6 hr after the stress. In leukocytopenic animals, levels 6 hr after stress were not lower than those preceding stress. Leukocytopenia markedly limited both the decrease in mucosal blood flow and the increase in gastric microvascular permeability. The level of gastric mucosal injury observed 6 hr after the stress was markedly attenuated by leukocytopenia. Pretreatment with neutrophil elastase inhibitors (ONO-5046 and Eglin C) or an anti-P-selectin monoclonal antibody produced effects similar to leukocytopenia. Neutrophil elastase is involved in the stress-induced gastric mucosal injury by decreasing gastric production of PGI2. Thus, pharmacologic inhibition of neutrophil elastase should help to prevent stress-induced gastric mucosal injury.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto, Japan

    Naoaki Harada, Kenji Okajima, Wenge Liu & Mitsuhiro Uchiba

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  1. Naoaki Harada
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  2. Kenji Okajima
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  3. Wenge Liu
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  4. Mitsuhiro Uchiba
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Harada, N., Okajima, K., Liu, W. et al. Activated Neutrophils Impair Gastric Cytoprotection: Role of Neutrophil Elastase. Dig Dis Sci 45, 1210–1216 (2000). https://doi.org/10.1023/A:1005518523095

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