Department of Pneumology, University Medical Clinic, Rostock, Germany.
Scand J Immunol. 2010 Apr;71(4):304-11. doi: 10.1111/j.1365-3083.2010.02375.x.
Lipopolysaccharides (LPS) have been associated with a protective role in the development of asthma while higher levels of endotoxin have been linked with more severe asthma. LPS recruit neutrophils and eosinophils and activate macrophages via the CD14 receptor. The soluble CD 14 receptor (sCD14) has been found in bronchoalveolar lavage fluid in different diseases including allergic asthma. To elucidate the kinetics and the regulation of sCD14 concentrations in BAL in asthma, 18 patients with allergic asthma underwent segmental allergen challenge at different time points (10 min, 18, 42 and 162 h). In addition, CD14(+) peripheral blood mononuclear cell (PBMC-CD14(+)) cultures from seven allergic and seven non-allergic subjects were stimulated with LPS, leukotrien D(4) (LTD(4)), a combination of LPS and LTD(4), IL-17 and LTD(4) in presence of the leukotriene-receptor antagonist (LTRA) Montelukast for 6, 12 and 24 h. sCD14 concentrations in BAL and the supernatants were measured by ELISA. sCD14 concentrations in BAL were significantly increased 18 h after allergen challenge and peaked at 42 h. At 162 h, concentrations had returned to baseline levels. In PBMC-CD14(+) cultures, sCD14 levels increased significantly 24 h after stimulation with LTD(4) and Montelukast was able to block LTD(4)-induced stimulation. Allergen challenge leads to a significant increase in sCD14 concentrations in BAL and might modulate the allergen-induced inflammation. In addition, LTD(4) might play a role in the release of sCD14, and it could be speculated that sCD14 reduction by LTRA might contribute to the mechanisms of LTRA in the treatment of allergic asthma.
脂多糖（LPS）与哮喘的发展具有保护作用有关，而内毒素水平较高则与更严重的哮喘有关。LPS 通过 CD14 受体招募中性粒细胞和嗜酸性粒细胞并激活巨噬细胞。可溶性 CD14 受体（sCD14）已在不同疾病的支气管肺泡灌洗液中发现，包括过敏性哮喘。为了阐明哮喘患者 BAL 中 sCD14 浓度的动力学和调节，18 名过敏性哮喘患者在不同时间点（10 分钟、18 小时、42 小时和 162 小时）进行了节段性过敏原挑战。此外，来自 7 名过敏性和 7 名非过敏性受试者的 CD14（+）外周血单核细胞（PBMC-CD14（+））培养物用 LPS、白三烯 D4（LTD4）、LPS 和 LTD4 的组合、IL-17 和 LTD4 刺激，在白三烯受体拮抗剂（LTRA）孟鲁司特的存在下刺激 6、12 和 24 小时。通过 ELISA 测量 BAL 和上清液中的 sCD14 浓度。过敏原挑战后 18 小时 BAL 中的 sCD14 浓度显着增加，并在 42 小时达到峰值。在 162 小时时，浓度已恢复到基线水平。在 PBMC-CD14（+）培养物中，LTD4 和孟鲁司特刺激后 24 小时 sCD14 水平显着增加，孟鲁司特能够阻断 LTD4 诱导的刺激。过敏原挑战导致 BAL 中 sCD14 浓度显着增加，可能调节过敏原诱导的炎症。此外，LTD4 可能在 sCD14 的释放中起作用，并且可以推测 LTRA 通过减少 sCD14 可能有助于 LTRA 在治疗过敏性哮喘中的机制。
