Protective effect of FUT-175 on pulmonary function of xenografts in a guinea pig-to-rat lung perfusion model
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概要
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Background: FUT-175 (nafamostat mesilate) has a variety of pharmacological effects; in addition to its stable potent serineprotease inhibitory activity, it exerts far stronger anti-complement activity than other protease inhibitors. Here, we evaluatedthe protective effect of FUT-175 on pulmonary function of xenografts in an ex vivo guinea pig-to-rat lung perfusion model,using a device for analyzing pulmonary function in small animals.Methods: Animals were divided into three groups (n = 6 each), Isograft (Group I), Xenograft (Group X), and Xenograft withFUT-175 (Group XF). In the latter, 10 mg of FUT-175 was added to the extracorporeal circuit before perfusion with xenogeneicblood was started. The following parameters were serially measured in these three groups: complement activity causing 50%hemolysis (CH50 units) in the perfusion blood either before or during perfusion, pulmonary arterial pressure, dynamic pulmonarycompliance, and airway resistance. In addition, Hematoxylin and Eosin staining of the lungs and assays of rat IgM, IgG,and anti-C3 deposition were carried out after perfusion.Results: The duration of satisfactory pulmonary function after the start of perfusion was significantly increased in Group XF.CH50 in Group XF decreased significantly than in Group X. In addition, FUT-175 suppressed both the increase in pulmonaryarterial pressure and airway resistance, and the decrease in dynamic pulmonary compliance. In Group XF, intraalveolar hemorrhageand the thickening of the arterial wall were not observed. Groups X and XF showed deposition of IgM, IgG, and C3at the endothelium of the pulmonary arteries but less in Group I.Conclusions: This study suggests that FUT-175 inhibited complement activation including the alternative pathway and improvedlung xenograft pulmonary function. FUT-175 ameliorates hyperacute rejection in a guinea pig-to-rat ex vivo xenogeneiclung perfusion model.
著者
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Ryu Chusei/tagawa
Division Of Surgical Oncology Department Of Translational Medical Science Nagasaki University Gradua
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Ryu Chusei
Division of Surgical Oncology, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences,