Role of neutrophil elastase in stress-induced gastric mucosal injury in rats. 1998

W Liu, and K Okajima, and K Murakami, and N Harada, and H Isobe, and T Irie
Department of Laboratory Medicine, Kumamoto University School of Medicine, and the Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.

Activated neutrophils play an important role in tissue injury by releasing various inflammatory mediators capable of damaging endothelial cells. To investigate whether neutrophil elastase (NE) is involved in stress-induced gastric mucosal injury, we examined the effects of 2 NE inhibitors (ONO-5046 and L-658 758) as well as nitrogen mustard-induced leukocytopenia on the formation of gastric mucosal lesions, gastric mucosal blood flow, gastric mucosal microvascular permeability, and gastric neutrophil accumulation in rats subjected to water immersion-restraint stress (WIR). Gastric mucosal injury peaked 8 hours after WIR. Gastric mucosal blood flow, as measured by laser-Doppler flow cytometry, decreased to 45% of its initial level 8 hours after WIR. Gastric mucosal microvascular permeability, evaluated by Evans blue dye leakage to the gastric mucosa, showed an increase, peaking 8 hours after WIR. Gastric accumulation of neutrophils, determined by measuring gastric myeloperoxidase activity and by histologic examination, was also significantly increased 8 hours after WIR. Both of the NE inhibitors markedly prevented the formation of gastric mucosal lesions. They also decreased the reduction in gastric mucosal blood flow seen in animals subjected to WIR while preventing increases in gastric mucosal microvascular permeability. Gastric neutrophil accumulation was significantly reduced in animals given either inhibitor 8 hours after WIR. Leukocytopenia produced effects similar to those produced by the inhibitors. Taken together, these observations strongly suggest that NE promotes stress-induced gastric mucosal injury in rats by reducing gastric mucosal blood flow and increasing neutrophil accumulation.

UI MeSH Term Description Entries
D007970 Leukopenia A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000). Leukocytopenia,Leukocytopenias,Leukopenias
D008297 Male Males
D008466 Mechlorethamine A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA. Chlorethazine,Chlormethine,Mechlorethamine Oxide,Mustine,Nitrogen Mustard,Nitrogen Mustard N-Oxide,Bis(2-chloroethyl)methylamine,Caryolysine,Cloramin,Embichin,Mechlorethamine Hydrochloride,Mechlorethamine Hydrochloride N-Oxide,Mechlorethamine N-Oxide,Methylchlorethamine,Mitomen,Mustargen,NSC-10107,NSC-762,Nitrogranulogen,Nitromin,Hydrochloride N-Oxide, Mechlorethamine,Hydrochloride, Mechlorethamine,Mechlorethamine Hydrochloride N Oxide,Mechlorethamine N Oxide,N-Oxide, Mechlorethamine Hydrochloride,N-Oxide, Nitrogen Mustard,NSC 10107,NSC 762,NSC10107,NSC762,Nitrogen Mustard N Oxide
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010437 Peptic Ulcer Ulcer that occurs in the regions of the GASTROINTESTINAL TRACT which come into contact with GASTRIC JUICE containing PEPSIN and GASTRIC ACID. It occurs when there are defects in the MUCOSA barrier. The common forms of peptic ulcers are associated with HELICOBACTER PYLORI and the consumption of nonsteroidal anti-inflammatory drugs (NSAIDS). Gastroduodenal Ulcer,Marginal Ulcer,Gastroduodenal Ulcers,Marginal Ulcers,Peptic Ulcers,Ulcer, Gastroduodenal,Ulcer, Marginal,Ulcer, Peptic,Ulcers, Gastroduodenal,Ulcers, Marginal,Ulcers, Peptic
D012149 Restraint, Physical Use of a device for the purpose of controlling movement of all or part of the body. Splinting and casting are FRACTURE FIXATION. Immobilization, Physical,Physical Restraint,Physical Immobilization,Physical Restraints,Restraints, Physical
D002199 Capillary Permeability The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement. Microvascular Permeability,Permeability, Capillary,Permeability, Microvascular,Vascular Permeability,Capillary Permeabilities,Microvascular Permeabilities,Permeabilities, Capillary,Permeabilities, Microvascular,Permeabilities, Vascular,Permeability, Vascular,Vascular Permeabilities
D002511 Cephalosporins A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. Antibiotics, Cephalosporin,Cephalosporanic Acid,Cephalosporin,Cephalosporin Antibiotic,Cephalosporanic Acids,Acid, Cephalosporanic,Acids, Cephalosporanic,Antibiotic, Cephalosporin,Cephalosporin Antibiotics
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

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