Bourke W J, O'Connor C M, FitzGerald M X, McDonnell T J
Dept of Medicine and Therapeutics, University College Dublin, Belfield, Eire.
Eur Respir J. 1994 Oct;7(10):1754-8. doi: 10.1183/09031936.94.07101754.
In pseudomonal septicaemia, serum levels of antibody to exotoxin A have been demonstrated to be an important independent predictor of survival. Previously, we have demonstrated that exotoxin A directly injures pulmonary endothelial cells, and that dibutyryl-cyclic adenosine monophosphate (Db-cAMP) can attenuate this injury. The object of this study was to examine the mechanisms of this pulmonary endothelial cell injury and the mechanism of Db-cAMP protection. The effects of differing duration of exposure to exotoxin A and a reduction in temperature on endothelial cell injury were examined. In addition, the effect of post-treatment with Db-cAMP on exotoxin A-induced endothelial cell injury was studied. A brief, 5 min, exposure to exotoxin resulted in maximum injury comparable to that produced by 18 h exposure. This injury did not occur at low temperatures, which would inhibit receptor-mediated endocytosis. Db-cAMP protected endothelial cells, even when added up to one hour after exotoxin exposure. These results suggest that, in this model, exotoxin A-induced injury of endothelial cells is receptor-mediated. Furthermore, this injury may be attenuated even after exotoxin A internalization has taken place.
在铜绿假单胞菌败血症中，血清中外毒素A抗体水平已被证明是生存的重要独立预测指标。此前，我们已证明外毒素A直接损伤肺内皮细胞，且二丁酰环磷腺苷（Db-cAMP）可减轻这种损伤。本研究的目的是探讨这种肺内皮细胞损伤的机制以及Db-cAMP保护作用的机制。研究了外毒素A不同暴露时间和温度降低对内皮细胞损伤的影响。此外，还研究了Db-cAMP后处理对外毒素A诱导的内皮细胞损伤的影响。短暂暴露于外毒素5分钟所导致的最大损伤程度与暴露18小时产生的损伤程度相当。这种损伤在低温下不会发生，因为低温会抑制受体介导的内吞作用。即使在外毒素暴露后长达一小时添加Db-cAMP，它仍能保护内皮细胞。这些结果表明，在该模型中，外毒素A诱导的内皮细胞损伤是受体介导的。此外，即使在外毒素A内化后，这种损伤也可能会减轻。
