Human Surfactant Protein SP-A1 and SP-A2 Variants Differentially Affect the Alveolar Microenvironment, Surfactant Structure, Regulation and Function of the Alveolar Macrophage, and Animal and Human Survival Under Various Conditions.

Human Surfactant Protein SP-A1 and SP-A2 Variants Differentially Affect the Alveolar Microenvironment, Surfactant Structure, Regulation and Function of the Alveolar Macrophage, and Animal and Human Survival Under Various Conditions.
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DOI:
10.3389/fimmu.2021.681639
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发表时间:
2021
影响因子:
7.3
通讯作者:
Phelps DS
Phelps DS
中科院分区:
医学2区
文献类型:
--
作者:
Floros J;Thorenoor N;Tsotakos N;Phelps DS

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人类先天宿主防御分子 SP-A1 和 SP-A2 变体对小鼠和肺移植患者感染后的存活率产生不同的影响。 SP-A 与肺泡中的前哨先天免疫细胞、肺泡巨噬细胞 (AM) 相互作用,并调节其功能和调节。 SP-A还在肺表面活性剂相关方面发挥作用,包括表面活性剂结构和重组。对于大多数(如果不是全部)肺部疾病,存在宿主防御和炎症过程失调和/或表面活性剂功能障碍或缺乏。由于 SP-A 在这两个一般过程中都发挥着作用,其中一个或两个可能在肺部疾病中变得异常,因此 SP-A 是健康和疾病中的重要分子。在人类中(与啮齿动物不同)SP-A 由两个基因(SFTPA1 和 SFTPA2)编码,并且每个基因都已被鉴定为具有广泛的遗传和表观遗传复杂性。在这篇综述中,我们重点关注两种 SP-A 基因特异性产物 SP-A1 和 SP-A2 及其相应变体之间的功能、结构和调控差异。我们讨论了这些变异对表面活性剂结构、肺泡微环境、上皮 II 型 miRNome 的调节、AM 的调节和功能、感染后生物体的总体生存等的不同影响。尽管已经有很多关于 SP-A 的评论,但这是第一次对人类 SP-A1 和 SP-A2 之间的差异进行如此全面的评论。
The human innate host defense molecules, SP-A1 and SP-A2 variants, differentially affect survival after infection in mice and in lung transplant patients. SP-A interacts with the sentinel innate immune cell in the alveolus, the alveolar macrophage (AM), and modulates its function and regulation. SP-A also plays a role in pulmonary surfactant-related aspects, including surfactant structure and reorganization. For most (if not all) pulmonary diseases there is a dysregulation of host defense and inflammatory processes and/or surfactant dysfunction or deficiency. Because SP-A plays a role in both of these general processes where one or both may become aberrant in pulmonary disease, SP-A stands to be an important molecule in health and disease. In humans (unlike in rodents) SP-A is encoded by two genes (SFTPA1 and SFTPA2) and each has been identified with extensive genetic and epigenetic complexity. In this review, we focus on functional, structural, and regulatory differences between the two SP-A gene-specific products, SP-A1 and SP-A2, and among their corresponding variants. We discuss the differential impact of these variants on the surfactant structure, the alveolar microenvironment, the regulation of epithelial type II miRNome, the regulation and function of the AM, the overall survival of the organism after infection, and others. Although there have been a number of reviews on SP-A, this is the first review that provides such a comprehensive account of the differences between human SP-A1 and SP-A2.
DOI: 10.1083/jcb.141.6.1301
发表时间: 1998-06-15
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影响因子: --
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