Ozawa T, Sugiyama S, Hayakawa M, Taki F
Department of Biomedical Chemistry and Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1991 Feb;29(2):159-64.
It is well known that pulmonary influx of neutrophils is involved in lung injury in patients with adult respiratory distress syndrome (ARDS). Neutrophils are major contributors to the self-defence mechanism, however, adverse effects of neutrophils have also been recognized. Recently, we found that a highly toxic substance, 9, 10-epoxy-12-octadecenoate (leukotoxin) is biosynthesized by human neutrophils. This study was designed to investigate whether or not leukotoxin participates in lung injury in ARDS and coagulation abnormality which is often associated with ARDS. Intravenous injection of leukotoxin (100 mumol/kg) caused acute edematous lung injury, which was evidenced by increased lung weight, albumin concentrations, and angiotensin converting enzyme activities in lung lavages. Pulmonary capillary endothelial damage and pulmonary edema were observed by electron microscopy. Moreover, considerable amounts of leukotoxin were detected in lung lavage fluid of rats exposed to pure oxygen for 60 h and patients with ARDS. An increased number of neutrophils and albumin concentrations were also observed in these lavage fluids. Intravenous injection of leukotoxin (100 mumol/kg) induced coagulation abnormalities such as disseminated intravascular coagulation. Increased levels of plasma leukotoxin were detected in ARDS patients with coagulation abnormalities. These results suggest that leukotoxin biosynthesized by neutrophils is an important contributor to lung injury in ARDS and associated coagulation abnormalities.
众所周知，中性粒细胞流入肺部参与了成人呼吸窘迫综合征（ARDS）患者的肺损伤。中性粒细胞是自我防御机制的主要贡献者，然而，中性粒细胞的不良影响也已得到认可。最近，我们发现一种剧毒物质，9,10-环氧-12-十八碳烯酸（白细胞毒素）是由人类中性粒细胞生物合成的。本研究旨在调查白细胞毒素是否参与ARDS的肺损伤以及常与ARDS相关的凝血异常。静脉注射白细胞毒素（100μmol/kg）导致急性肺水肿性肺损伤，这通过肺重量增加、肺灌洗中的白蛋白浓度和血管紧张素转换酶活性增加得到证实。通过电子显微镜观察到肺毛细血管内皮损伤和肺水肿。此外，在暴露于纯氧60小时的大鼠和ARDS患者的肺灌洗液中检测到大量白细胞毒素。在这些灌洗液中还观察到中性粒细胞数量增加和白蛋白浓度升高。静脉注射白细胞毒素（100μmol/kg）诱导凝血异常，如弥散性血管内凝血。在有凝血异常的ARDS患者中检测到血浆白细胞毒素水平升高。这些结果表明，中性粒细胞生物合成的白细胞毒素是ARDS肺损伤和相关凝血异常的重要促成因素。
