The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.
The Alpha-Tocopherol Form of Vitamin E Boosts Elastase Activity of Human PMNs and Their Ability to Kill Streptococcus pneumoniae.
复制标题
DOI：
10.3389/fcimb.2017.00161
复制
发表时间：
2017
影响因子：
5.7
通讯作者：
Panda A
中科院分区：
文献类型：
--
作者：
Bou Ghanem EN;Lee JN;Joma BH;Meydani SN;Leong JM;Panda A
尽管有疫苗，肺炎链球菌仍然是威胁生命的感染，如肺炎，菌血症和脑膜炎的主要原因。多形核白细胞（PMN）是疾病过程的关键决定因素，因为最佳的宿主防御需要一个初始的强大的肺PMN反应，以控制细菌数量，然后在感染后期调节这种反应。老年人免疫功能普遍下降，基础炎症水平较高，患肺炎球菌性肺炎的风险增加。使用老年小鼠感染模型，我们先前表明，口服补充α-生育酚形式的维生素E（α-Toc）可减少肺部炎症，部分通过调节中性粒细胞穿过肺上皮迁移到肺泡腔，并逆转与年龄相关的对肺炎球菌肺炎的抵抗力下降。本研究的目的是检测α-Toc对分离自年轻（22-35岁）或老年（65-69岁）个体的中性粒细胞响应S.肺炎并杀死补体调理的肺炎球菌。我们发现，肺炎球菌诱导的跨上皮细胞迁移的基础水平从年轻或老年供体的中性粒细胞是无法区分的，这表明，与年龄相关的肺部炎症的恶化是由于老年人的中性粒细胞的内在属性，而是可能反映了老年人的肺部炎症环境。与其抗炎活性一致，无论供体年龄如何，α-Toc治疗均可减少PMN迁移。出乎意料的是，与先前的研究显示抗体调理细菌的杀伤效果差不同，我们发现老年供体的PMN在体外杀死补体调理细菌方面比年轻供体更有效。我们还发现，老年供体的中性粒细胞抗菌活性增强与中性粒细胞弹性蛋白酶活性增加相关，中性粒细胞弹性蛋白酶是一种丝氨酸蛋白酶，是杀死肺炎球菌所必需的。值得注意的是，与α-Toc孵育增加了年轻供体的PMN弹性蛋白酶活性，并增强了其杀死补体调理肺炎球菌的能力。这些发现表明，α-Toc是PMN反应的有效调节剂，是对抗肺炎球菌感染的潜在营养干预措施。
Despite the availability of vaccines, Streptococcus pneumoniae remains a leading cause of life-threatening infections, such as pneumonia, bacteremia and meningitis. Polymorphonuclear leukocytes (PMNs) are a key determinant of disease course, because optimal host defense requires an initial robust pulmonary PMN response to control bacterial numbers followed by modulation of this response later in infection. The elderly, who manifest a general decline in immune function and higher basal levels of inflammation, are at increased risk of developing pneumococcal pneumonia. Using an aged mouse infection model, we previously showed that oral supplementation with the alpha-tocopherol form of vitamin E (α-Toc) decreases pulmonary inflammation, in part by modulating neutrophil migration across lung epithelium into alveolar spaces, and reverses the age-associated decline in resistance to pneumococcal pneumonia. The objective of this study was to test the effect of α-Toc on the ability of neutrophils isolated from young (22–35 years) or elderly (65–69 years) individuals to migrate across epithelial cell monolayers in response to S. pneumoniae and to kill complement-opsonized pneumococci. We found that basal levels of pneumococcal-induced transepithelial migration by PMNs from young or elderly donors were indistinguishable, suggesting that the age-associated exacerbation of pulmonary inflammation is not due to intrinsic properties of PMNs of elderly individuals but rather may reflect the inflammatory milieu of the aged lung. Consistent with its anti-inflammatory activity, α-Toc treatment diminished PMN migration regardless of donor age. Unexpectedly, unlike previous studies showing poor killing of antibody-opsonized bacteria, we found that PMNs of elderly donors were more efficient at killing complement-opsonized bacteria ex vivo than their younger counterparts. We also found that the heightened antimicrobial activity in PMNs from older donors correlated with increased activity of neutrophil elastase, a serine protease that is required to kill pneumococci. Notably, incubation with α-Toc increased PMN elastase activity from young donors and boosted their ability to kill complement-opsonized pneumococci. These findings demonstrate that α-Toc is a potent modulator of PMN responses and is a potential nutritional intervention to combat pneumococcal infection.