Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats.
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.
Jian
Ming-Yuan
MY
First Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi Matsumoto 390-8621, Japan.
Koizumi
Tomonobu
T
Tsushima
Kenji
K
Fujimoto
Keisaku
K
Kubo
Keishi
K
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
D013449:Sulfonamides; D016179:Granulocyte Colony-Stimulating Factor; C069195:sivelestat; D019272:Leukocyte Elastase; D006851:Hydrochloric Acid; D005998:Glycine