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Nafamostat mesilate attenuates radical formation in the rat lung infused with endotoxin
Yoshihiro Minamiya1, Satoshi Saito, Masakatsu Nakamura
1Second Department of Surgery, Akita University School of Medicine, Akita City, Japan.
Abstract:
We previously reported direct evidence of respiratory bursting by neutrophils in the pulmonary circulation of endotoxin-infused rats. To evaluate the effect of the protease inhibitor nafamostat mesilate (NM) on leukocyte-mediated radical formation in the pulmonary circulation of rats infused with endotoxin, we observed and measured the number of sticking leukocytes and quantified radical production in the pulmonary circulation of endotoxin-infused rats by means of a fluorescent imaging technique. Plasma C3a (desArg) was also measured using an enzyme-linked immunosorbent assay. Three groups (n = 5) of rats were infused with 4.5 mg/kg/h endotoxin (Et group), 50 microg/kg/h NM + endotoxin (NM group), or physiological saline (Ct group) for 2 h. The number of the leukocytes adhering within pulmonary capillaries, oxygen radical production in the rat pulmonary circulation, and plasma C3a (desArg) were all lower in the NM group than in the Et group. The leukocytes producing oxygen radicals were confirmed to be neutrophils by electron microscopic analysis of cerium deposition. We conclude that NM attenuates plasma C3a formation, neutrophil adherence to pulmonary capillaries, and their production of oxygen radical in rats infused with endotoxin.
Insights
Nafamostat mesilate (NM) reduces radical formation by neutrophils in the lungs of endotoxin-infused rats. This protease inhibitor treatment also decreased neutrophil adherence and plasma C3a levels, suggesting a protective effect.
Area of Science:
- Pulmonary circulation research
- Inflammation and immunology
- Pharmacology
Background:
- Neutrophils exhibit respiratory bursting in pulmonary circulation during endotoxemia.
- Protease inhibitors may modulate leukocyte-mediated radical formation.
Purpose of the Study:
- To evaluate the effect of nafamostat mesilate (NM) on leukocyte-mediated radical formation in endotoxin-infused rats.
- To assess NM's impact on neutrophil adherence and plasma C3a levels in this model.
Main Methods:
- Rats were infused with endotoxin, nafamostat mesilate + endotoxin, or saline.
- Leukocyte adherence, radical production (fluorescent imaging), and plasma C3a (ELISA) were measured.
- Electron microscopy confirmed neutrophil involvement in radical production.
Main Results:
- Nafamostat mesilate significantly reduced leukocyte adherence in pulmonary capillaries.
- Oxygen radical production in the pulmonary circulation was lower in the NM group.
- Plasma C3a (desArg) levels were attenuated by NM treatment.
Conclusions:
- Nafamostat mesilate attenuates endotoxin-induced plasma C3a formation.
- NM reduces neutrophil adherence to pulmonary capillaries.
- NM decreases oxygen radical production by neutrophils in endotoxemic rats.
