老年人口,估计到2050年翻一番,呼吸道感染和其他肺部疾病的风险增加。随着年龄的增长,肺泡内膜液(ALF)和肺泡隔室细胞中的生化变化可以改变局部免疫反应。为入侵的病原体创造机会,以建立成功的感染。的确,老年人的肺泡间隙是促炎的,促氧化,失调的环境仍未得到充分研究。我们进行了一次探索,ALF中可溶性蛋白质的定量蛋白质组学分析,深入了解分子指纹,通路,以及以老年人肺泡空间为特征的监管网络,与年轻人相比。我们鉴定出457种蛋白质在老年ALF中显著差异表达,包括增加基质金属蛋白酶的产量,细胞衰老的标记,抗菌药物,和嗜中性颗粒来源的蛋白质,其中,这表明,随着年龄的增长,老年人肺部的嗜中性粒细胞可能是导致肺泡环境失调的潜在因素.最后,我们描述了一个由血清反应因子介导的假想调节网络,该网络可以解释在老年人群中观察到的嗜中性粒细胞分布.
The older adult population, estimated to double by 2050, is at increased risk of respiratory infections and other pulmonary diseases. Biochemical changes in the lung alveolar lining fluid (ALF) and in alveolar compartment cells can alter local immune responses as we age, generating opportunities for invading pathogens to establish successful infections. Indeed, the lung alveolar space of older adults is a pro-inflammatory, pro-oxidative, dysregulated environment that remains understudied. We performed an exploratory, quantitative proteomic profiling of the soluble proteins present in ALF, developing insight into molecular fingerprints, pathways, and regulatory networks that characterize the alveolar space in old age, comparing it to that of younger individuals. We identified 457 proteins that were significantly differentially expressed in older adult ALF, including increased production of matrix metalloproteinases, markers of cellular senescence, antimicrobials, and proteins of neutrophilic granule origin, among others, suggesting that neutrophils in the lungs of older adults could be potential contributors to the dysregulated alveolar environment with increasing age. Finally, we describe a hypothetical regulatory network mediated by the serum response factor that could explain the neutrophilic profile observed in the older adult population.