Phelps David S, Umstead Todd M, Floros Joanna
The Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
The Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA, USA; Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
J Proteomics. 2014 Aug 28;108:427-44. doi: 10.1016/j.jprot.2014.06.007. Epub 2014 Jun 18.
Surfactant protein A (SP-A) is involved in lung innate immunity. Humans have two SP-A genes, SFTPA1 and SFTPA2, each with several variants. We examined the in vivo effects of treatment with specific SP-A variants on the alveolar macrophage (AM) proteome from SP-A knockout (KO) mice. KO mice received either SP-A1, SP-A2, or both. AM were collected and their proteomes examined with 2D-DIGE. We identified 90 proteins and categorized them as related to actin/cytoskeleton, oxidative stress, protease balance/chaperones, regulation of inflammation, and regulatory/developmental processes. SP-A1 and SP-A2 had different effects on the AM proteome and these effects differed between sexes. In males more changes occurred in the oxidative stress, protease/chaperones, and inflammation groups with SP-A2 treatment than with SP-A1. In females most SP-A1-induced changes were in the actin/cytoskeletal and oxidative stress groups. We conclude that after acute SP-A1 and SP-A2 treatment, sex-specific differences were observed in the AM proteomes from KO mice, and that these sex differences differ in response to SP-A1 and SP-A2. Females are more responsive to SP-A1, whereas the gene-specific differences in males were minimal. These observations not only demonstrate the therapeutic potential of exogenous SP-A, but also illustrate sex- and gene-specific differences in the response to it.
This study shows that changes occur in the alveolar macrophage proteome in response to a single in vivo treatment with exogenous SP-A1 and/or SP-A2. We demonstrate that SP-A1 and SP-A2 have different effects on the AM proteome and that sex differences exist in the response to each SP-A1 and SP-A2 gene product. This study illustrates the potential of exogenous SP-A1 and SP-A2 treatment for the manipulation of macrophage function and indicates that the specific SP-A variant used for treatment may vary with sex and with the cellular functions being modified. The observed changes may contribute to sex differences in the incidence of some lung diseases.
表面活性蛋白A（SP-A）参与肺部固有免疫。人类有两个SP-A基因，即SFTPA1和SFTPA2，每个基因都有多个变体。我们研究了用特定SP-A变体处理对SP-A基因敲除（KO）小鼠肺泡巨噬细胞（AM）蛋白质组的体内影响。KO小鼠接受SP-A1、SP-A2或两者同时处理。收集AM并通过二维差异凝胶电泳（2D-DIGE）检测其蛋白质组。我们鉴定出90种蛋白质，并将它们分类为与肌动蛋白/细胞骨架、氧化应激、蛋白酶平衡/伴侣蛋白、炎症调节以及调节/发育过程相关的蛋白质。SP-A1和SP-A2对AM蛋白质组有不同影响，且这些影响在性别之间存在差异。在雄性中，与SP-A1处理相比，SP-A2处理在氧化应激、蛋白酶/伴侣蛋白和炎症组中引起的变化更多。在雌性中，大多数SP-A1诱导的变化发生在肌动蛋白/细胞骨架和氧化应激组中。我们得出结论，在急性SP-A1和SP-A2处理后，在KO小鼠的AM蛋白质组中观察到了性别特异性差异，并且这些性别差异在对SP-A1和SP-A2的反应中有所不同。雌性对SP-A1的反应更敏感，而雄性中的基因特异性差异最小。这些观察结果不仅证明了外源性SP-A的治疗潜力，还说明了对其反应中的性别和基因特异性差异。
本研究表明，单次体内外源性SP-A1和/或SP-A2处理会导致肺泡巨噬细胞蛋白质组发生变化。我们证明SP-A1和SP-A2对AM蛋白质组有不同影响，并且对每个SP-A1和SP-A2基因产物的反应存在性别差异。本研究说明了外源性SP-A1和SP-A2处理对巨噬细胞功能调控的潜力，并表明用于治疗的特定SP-A变体可能因性别和被修饰的细胞功能而异。观察到的变化可能导致某些肺部疾病发病率的性别差异。
