Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA.
J Trauma Acute Care Surg. 2012 Apr;72(4):908-15. doi: 10.1097/TA.0b013e3182468989.
Laboratory and clinical studies demonstrated a salutary effect of estradiol (E2) on pneumonia and other infectious complications after trauma, while dihydrotestosterone (DHT) failed to show a similar effect. Secretory immunoglobulin A is the principle antibody in the respiratory and other mucosal secretions. Immunoglobulin A (IgA) production and transport into the mucosal secretion is regulated by Toll-like receptor 4 (TLR-4). In addition, E2 may influence immune regulatory cells via TLR-4. We hypothesized that the protective effect of E2 on the development of pneumonia may be related to modulation of IgA transport into respiratory secretions.
Calu-3 respiratory epithelial cell monolayers were established in a two-chamber cell culture system. Calu-3 cells were then treated with either E2 or DHT for 3 days for maximal cell stimulation. Dimeric IgA was added to the basal chamber of Calu-3 cells, and IgA transcellular transport was indexed by recovery of secretory immunoglobulin A in the apical chamber media. In separate experiments, Klebsiella pneumonia (10(5) CFU/mL) was added to the apical chamber of treated Calu-3 cell monolayers, and bacterial passage across Calu-3 cells was determined by bacterial recovery from the basal chamber. Calu-3 cells not treated with E2 or DHT served as control.
Calu-3 cells pretreated with E2 significantly increased IgA transport, and this effect was augmented in a dose-dependent fashion. Only cells pretreated with E2 significantly decreased bacterial passage, and this effect was exhibited in a dose- and time-dependent fashion. E2 led to a significant increase in TLR-4 expression.
The protective effect of E2 against pneumonia may be related to augmented transport of IgA into the respiratory mucosal secretions.
实验室和临床研究表明，雌二醇（E2）对创伤后肺炎和其他感染性并发症有有益影响，而二氢睾酮（DHT）则没有表现出类似的效果。分泌型免疫球蛋白 A 是呼吸道和其他黏膜分泌物中的主要抗体。免疫球蛋白 A（IgA）的产生和转运到黏膜分泌物受 Toll 样受体 4（TLR-4）调节。此外，E2 可能通过 TLR-4 影响免疫调节细胞。我们假设 E2 对肺炎发展的保护作用可能与调节 IgA 转运到呼吸道分泌物有关。
在双层细胞培养系统中建立 Calu-3 呼吸道上皮细胞单层。然后，用 E2 或 DHT 处理 Calu-3 细胞 3 天以达到最大细胞刺激。将二聚体 IgA 加入 Calu-3 细胞的基底室，通过在顶端室培养基中回收分泌型免疫球蛋白 A 来测定 IgA 的跨细胞转运。在单独的实验中，将肺炎克雷伯菌（10（5）CFU/mL）加入处理后的 Calu-3 细胞单层的顶端室，通过从基底室回收细菌来确定细菌穿过 Calu-3 细胞的情况。未用 E2 或 DHT 处理的 Calu-3 细胞作为对照。
用 E2 预处理的 Calu-3 细胞显著增加了 IgA 的转运，且这种作用呈剂量依赖性增强。只有用 E2 预处理的细胞显著降低了细菌的穿过，且这种作用呈剂量和时间依赖性。E2 导致 TLR-4 表达显著增加。
E2 对肺炎的保护作用可能与 IgA 向呼吸道黏膜分泌物中的转运增加有关。
