School of Medicine, Nanjing University, Nanjing, China.
Respirology. 2011 Apr;16(3):508-16. doi: 10.1111/j.1440-1843.2010.01920.x.
Airway bacterial infections pose a significant challenge to the management of COPD, a disease mainly caused by cigarette smoking. However, the mechanisms of impaired airway mucosal innate immunity against bacteria in COPD remain unclear. We examined the effect of cigarette smoke on prostaglandin E(2) (PGE(2)) and downstream epithelial host defence mechanisms including the antimicrobial substance human β-defensin-2 (hBD-2).
Brushed bronchial epithelial cells were obtained from healthy smokers and individuals with COPD, and cultured under air-liquid interface conditions with or without exposure to whole cigarette smoke (WCS) or Moraxella catarrhalis (Mc) infection. Bacterial load, hBD-2 (a molecule known to kill Mc) and PGE(2) were measured.
WCS decreased Mc-induced hBD-2 expression and increased Mc load on bronchial epithelial cells from healthy smokers and COPD patients. Moreover, WCS inhibited PGE(2) induction following Mc. PGE(2) was shown to increase hBD-2 production in bronchial epithelial cells from healthy smokers, but not from COPD patients.
The results suggest that in well-differentiated human bronchial epithelial cells, WCS may impair host defence against Mc in part through inhibiting PGE(2) production.
气道细菌感染是 COPD （主要由吸烟引起的疾病）管理的重大挑战。然而，COPD 患者气道黏膜先天免疫对细菌的损伤机制仍不清楚。我们研究了香烟烟雾对前列腺素 E2 （PGE2）的影响，以及包括抗菌物质人β防御素-2 （hBD-2）在内的下游上皮宿主防御机制。
从健康吸烟者和 COPD 患者中获取刷状支气管上皮细胞，并在气液界面条件下培养，同时或不暴露于全香烟烟雾（WCS）或卡他莫拉菌（Mc）感染。测量细菌负荷、hBD-2（已知能杀死 Mc 的分子）和 PGE2。
WCS 降低了 Mc 诱导的健康吸烟者和 COPD 患者支气管上皮细胞 hBD-2 的表达，并增加了 Mc 的负荷。此外，WCS 抑制了 Mc 后的 PGE2 诱导。PGE2 可增加健康吸烟者支气管上皮细胞的 hBD-2 产生，但不能增加 COPD 患者的 hBD-2 产生。
结果表明，在分化良好的人支气管上皮细胞中，WCS 可能通过抑制 PGE2 的产生，部分损害宿主对 Mc 的防御。
