Perl Mario, Lomas-Neira Joanne, Chung Chun-Shiang, Ayala Alfred
Department of Traumatology, Hand- and Reconstructive Surgery, University of Ulm Medical School, Ulm, Germany.
Mol Med. 2008 Jul-Aug;14(7-8):465-75. doi: 10.2119/2008-00011.Perl.
In spite of protective ventilatory strategies, Acute Lung Injury (ALI) remains associated with high morbidity and mortality. One reason for the lack of therapeutic options might be that ALI is a co-morbid event associated with a diverse family of diseases and, thus, may be the result of distinct pathological processes. Among them, activated neutrophil- (PMN-) induced tissue injury and epithelial cell apoptosis mediated lung damage represent two potentially important candidate pathomechanisms that have been put forward. Several approaches have been undertaken to test these hypotheses, with substantial success in the treatment of experimental forms of ALI. With this in mind, we will summarize these two current hypotheses of ALI briefly, emphasizing the role of apoptosis in regulating PMN and/or lung epithelial cell responses. In addition, the contribution that Fas-mediated inflammation may play as a potential biological link between lung cell apoptosis and PMN recruitment will be considered, as well as the in vivo application of small interfering RNA (siRNA) as a novel approach to the inhibition of ALI and its therapeutic implications.
尽管有保护性通气策略，但急性肺损伤（ALI）仍然与高发病率和高死亡率相关。缺乏治疗选择的一个原因可能是，ALI是一种与多种疾病相关的合并症事件，因此可能是不同病理过程的结果。其中，活化的中性粒细胞（PMN）诱导的组织损伤和上皮细胞凋亡介导的肺损伤代表了两种已被提出的潜在重要候选发病机制。已经采取了几种方法来检验这些假设，在治疗实验性ALI方面取得了显著成功。考虑到这一点，我们将简要总结目前关于ALI的这两种假设，强调凋亡在调节PMN和/或肺上皮细胞反应中的作用。此外，还将考虑Fas介导的炎症作为肺细胞凋亡与PMN募集之间潜在生物学联系可能发挥的作用，以及小干扰RNA（siRNA）作为一种抑制ALI的新方法及其治疗意义的体内应用。
