A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster.
We have examined the effect of ONO-5046.Na, a synthetic specific inhibitor of neutrophil elastase, on lipopolysaccharide (LPS)-induced acute lung inflammation. Syrian golden hamsters were injected intraperitoneally with either 300 mg.kg-1 of ONO-5046.Na or saline, 30 min before and 1 h after intratracheal administration of 0.1 mg.kg-1 LPS. Animals were sacrificed 2 and 24 h later and the wet-to-dry lung weight ratio (W/D) was determined. Bronchoalveolar lavage (BAL) was performed, and tissue sections were examined histologically. The effect of ONO-5046.Na on migration of isolated neutrophils was determined. W/D was not significantly different at 2 h, but was increased at 24 h in the LPS-treated animals. This increase was attenuated in the LPS-treated animals injected with ONO-5046.Na. Analysis of BAL fluid revealed that both at 2 and 24 h after LPS administration the total cell number and neutrophil number, albumin concentration, and elastase-like activity were significantly lower in the LPS-treated animals injected with ONO-5046.Na than in those given LPS alone. Histological examination of the lungs of the animals treated with LPS alone showed intra-alveolar haemorrhages and inflammatory cell infiltration 24 h after LPS administration, whereas the lungs of the LPS-treated ONO-5046.Na injected animals were only sparsely infiltrated by inflammatory cells, as indicated by the inflammation score.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D002634:Chemotaxis, Leukocyte; D006224:Cricetinae; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019272:Leukocyte Elastase; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000502:physiology; D009929:Organ Size; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011014:Pneumonia / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology*
D008070:Lipopolysaccharides; D013449:Sulfonamides; C069195:sivelestat; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D005998:Glycine