The Role of Complement Component C3 in Protection Against Pseudomonas Pneumonia-Induced Lung Injury.
The Role of Complement Component C3 in Protection Against Pseudomonas Pneumonia-Induced Lung Injury.
复制标题
补体成分 C3 在预防假单胞菌肺炎引起的肺损伤中的作用。
DOI：
10.1089/dna.2023.0445
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发表时间：
2024
影响因子：
3.1
通讯作者：
Kulkarni,HrishikeshS
中科院分区：
文献类型：
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作者：
Sahu,SanjayaK;Maurya,RahulK;Kulkarni,HrishikeshS
补体系统是通过攻击微生物以减少病原体负担来促进免疫抵抗的蛋白质家族。因此，某些补体蛋白的缺乏会导致反复的细菌感染，也会导致急性肺损伤（ALI）。我们和其他人已经表明，C3存在于免疫和非免疫细胞中，并调节细胞功能，如代谢，分化，细胞因子的产生和生存。尽管补体系统的新作用对宿主对ALI的反应有影响，但关键问题仍然存在于肺上皮细胞。在这篇综述中，我们总结了我们最近的文章中，我们报道了在铜绿假单胞菌诱导的ALI，肺上皮细胞来源的C3的运作独立于肝来源的C3。具体而言，我们报告了使用人类细胞培养系统和全球以及条件性基因敲除小鼠模型的组合，以证明肺上皮细胞来源的C3的中心性。我们还总结了最近的文章，询问了细胞内和/或本地衍生的C3在宿主防御中的作用。我们认为，C3是一个非常有吸引力的候选人，用于增强肺损伤中的组织弹性，因为它有助于肺上皮细胞的存活和功能，这是一种促进屏障功能的关键细胞类型。
The complement system is a family of proteins that facilitate immune resistance by attacking microbes to decrease pathogen burden. As a result, deficiencies of certain complement proteins result in recurrent bacterial infections, and can also result in acute lung injury (ALI). We and others have shown that C3 is present in both immune and nonimmune cells, and modulates cellular functions such as metabolism, differentiation, cytokine production, and survival. Although the emerging roles of the complement system have implications for host responses to ALI, key questions remain vis-a-vis the lung epithelium. In this review, we summarize our recent article in which we reported that duringPseudomonas aeruginosa-induced ALI, lung epithelial cell-derived C3 operates independent of liver-derived C3. Specifically, we report the use of a combination of human cell culture systems and global as well as conditional knockout mouse models to demonstrate the centrality of lung epithelial cell-derived C3. We also summarize recent articles that have interrogated the role of intracellular and/or locally derived C3 in host defense. We propose that C3 is a highly attractive candidate for enhancing tissue resilience in lung injury as it facilitates the survival and function of the lung epithelium, a key cell type that promotes barrier function.