Neutrophil elastase inhibitor (sivelestat) attenuates subsequent ventilator-induced lung injury in mice. 2007

Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan.

Mechanical ventilation can paradoxically cause acute lung injury, which is termed ventilator-induced lung injury. Neutrophil recruitment and neutrophil elastase release play a central role in the pathogenesis of ventilator-induced lung injury including cell damage, extracellular matrix degradation and alveolar-capillary hyperpermeability. We therefore speculated that neutrophil elastase inhibition ameliorates ventilator-induced lung injury. Anesthetized C57/BL6 mice received mechanical ventilation with a high tidal volume (V(T); 20 ml/kg) for 4 h. The neutrophil elastase inhibitor (sivelestat, 100 mg/kg) or saline was given intraperitoneally (i.p.) 30 min before ventilation. Sivelestat completely inhibited both neutrophil elastase and myeloperoxidase activities that were increased by ventilation, and attenuated the histopathological degree of lung damage, neutrophil accumulation and lung water content, as well as the concentration of macrophage inflammatory protein (MIP)-2, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid and serum. Moreover, mechanical ventilation increased the phosphorylation of c-Jun NH2-terminal kinase (JNK) and the expression of early growth response gene-1 (Egr-1) mRNA, and these increases were also recovered by sivelestat. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed apoptotic cells mainly in alveolar epithelial cells and their numbers corresponded to histological damage. These data suggested that sivelestat could protect against ventilator-induced lung injury by suppressing apoptotic responses through mechanical stress-induced cell signaling in addition to inhibiting neutrophil chemotaxis.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008171 Lung Diseases Pathological processes involving any part of the LUNG. Pulmonary Diseases,Disease, Pulmonary,Diseases, Pulmonary,Pulmonary Disease,Disease, Lung,Diseases, Lung,Lung Disease
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
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
D011654 Pulmonary Edema Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening. Wet Lung,Edema, Pulmonary,Edemas, Pulmonary,Pulmonary Edemas,Lung, Wet,Lungs, Wet,Wet Lungs
D012122 Ventilators, Mechanical Mechanical devices used to produce or assist pulmonary ventilation. Mechanical Ventilator,Mechanical Ventilators,Respirators,Ventilators, Pulmonary,Pulmonary Ventilator,Pulmonary Ventilators,Ventilator, Pulmonary,Ventilators,Respirator,Ventilator,Ventilator, Mechanical
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium

Related Publications

Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
January 2023, Frontiers in immunology,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
January 2023, Frontiers in immunology,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
September 2016, International journal of molecular medicine,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
January 2007, The Annals of thoracic surgery,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
April 2024, Heliyon,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
October 2020, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
April 2013, Molecular medicine reports,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
April 2017, Biochemical and biophysical research communications,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
February 2007, International journal of molecular medicine,
Akihiro Sakashita, and Yoshihiro Nishimura, and Teruaki Nishiuma, and Kaori Takenaka, and Kazuyuki Kobayashi, and Yoshikazu Kotani, and Mitsuhiro Yokoyama
February 2005, Shock (Augusta, Ga.),
Copied contents to your clipboard!