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细菌毒素诱导的肺上皮细胞毒性及二丁酰环磷腺苷的保护作用

Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective effect of dibutyryl-cAMP.

作者信息

Bourke W, Kamp D, Dunn M, Chang S W

机构信息

Department of Medicine, Northwestern University Medical School, Chicago, IL, USA.

出版信息

Ir J Med Sci. 1998 Jan-Mar;167(1):19-21. doi: 10.1007/BF02937547.

DOI:10.1007/BF02937547
PMID:9540293
Abstract

Bacterial infection is the most common cause of the adult respiratory distress syndrome which, in turn is associated with endothelial capillary permeability and alveolar oedema. Previously, we have demonstrated the direct cytotoxicity of the bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells. The purpose of this study was to investigate the effect of Exo A and LPS on pulmonary epithelial cells in vitro. We also tested the protective effect of dibutyryl cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity. In cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as measured by 51Cr release from these cells. LPS did not injure RAEC's. Pretreatment of RAEC with db-cAMP (1 mM) attenuated Exo A induced cytotoxicity. We conclude that (1) Exo A directly injures epithelial lung cells and may contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar epithelial cells in this model are resistant to LPS induced injury.

摘要

细菌感染是成人呼吸窘迫综合征最常见的病因,而成人呼吸窘迫综合征又与内皮毛细血管通透性及肺泡水肿相关。此前,我们已证明铜绿假单胞菌外毒素A(Exo A)和肠炎沙门氏菌脂多糖(LPS)这两种细菌毒素对肺内皮细胞具有直接细胞毒性。本研究旨在探讨Exo A和LPS对体外培养的肺上皮细胞的影响。我们还测试了二丁酰环磷酸腺苷(db-cAMP)对Exo A诱导的细胞毒性的保护作用。在培养的大鼠肺泡上皮细胞(RAEC)中,Exo A可导致细胞毒性,这可通过这些细胞释放51Cr来测定。LPS不会损伤RAEC。用db-cAMP(1 mM)预处理RAEC可减轻Exo A诱导的细胞毒性。我们得出以下结论:(1)Exo A可直接损伤肺上皮细胞,在细菌感染情况下可能导致肺损伤;(2)db-cAMP可保护肺泡上皮细胞免受Exo A诱导的细胞毒性;(3)在该模型中,肺泡上皮细胞对LPS诱导的损伤具有抗性。

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本文引用的文献

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Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity: protection by dibutyryl-cAMP.铜绿假单胞菌外毒素A诱导肺内皮细胞毒性:二丁酰环磷腺苷的保护作用。
Eur Respir J. 1994 Oct;7(10):1754-8. doi: 10.1183/09031936.94.07101754.
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