title: Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats.
abstract: It has been suggested that neutrophils play an important role in acid-aspirated lung injury. We examined the effects of the high dose of granulocyte-colony stimulating factor (G-CSF), which is capable of increasing peripheral neutrophils, and a specific neutrophil elastase inhibitor (ONO-5046) on acid lung injury in rats. Animals were anesthetized and normal saline (NS, 2 mL kg(-1)) or hydrochloric acid (HCl, 0.1 N 2 mL kg(-1)) was then instilled into trachea. Thirty minutes before HCl instillation, G-CSF (150 microg kg(-1)) was injected subcutaneously or ONO-5046 (10 mg kg(-1) h(-1)) was infused continuously into the right jugular vein. Animals were ventilated during the experiments. Five hours after HCl or NS instillation, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. Total nuclear cell count, absorbance, albumin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC), neutrophil elastase in BALF, wet-to-dry (W/D) ratio were measured. HCl aspiration markedly increased these values in BALF and W/D ratio. Both ONO-5046 and G-CSF attenuated the parameters increased by acid-induced lung injury in rats. The data suggests that neutrophils play an important role in acid-induced lung injury. However, high-dose G-CSF does not exacerbate acid-aspirated lung injury in rats, although this agent causes an increase in peripheral neutrophils.
authors.affiliation: First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi Matsumoto 390-8621, Japan.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Jian
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Koizumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsushima
authors.forename: Keisaku
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000009:adverse effects; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D011015:Pneumonia, Aspiration / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D013449:Sulfonamides; D016179:Granulocyte Colony-Stimulating Factor; C069195:sivelestat; D019272:Leukocyte Elastase; D006851:Hydrochloric Acid; D005998:Glycine