Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-University Marburg, Marburg, Germany.
Eur J Immunol. 2010 Apr;40(4):1118-26. doi: 10.1002/eji.200939275.
The human cathelicidin antimicrobial peptide acts as an effector molecule of the innate immune system with direct antimicrobial and immunomodulatory effects. The aim of this study was to test whether the cathelicidin LL-37 modulates the response of neutrophils to microbial stimulation. Human neutrophils were exposed to LPS, Staphylococcus aureus and Pseudomonas aeruginosa subsequent to incubation with LL-37 and cytokine release was measured by ELISA. The incubation with LL-37 significantly decreased the release of proinflammatory cytokines from stimulated human neutrophils. ROS production of neutrophils was determined by a luminometric and a flow cytometry method. The peptide induced the production of ROS and the engulfment of bacteria into neutrophils. Peritoneal mouse neutrophils isolated from CRAMP-deficient and WT animals were treated with LPS and TNF-alpha in the supernatant was measured by ELISA. Antimicrobial activity of neutrophils was detected by incubating neutrophils isolated from CRAMP-knockout and WT mice with bacteria. Neutrophils from CRAMP-deficient mice released significantly more TNF-alpha after bacterial stimulation and showed decreased antimicrobial activity as compared to cells from WT animals. In conclusion, LL-37 modulates the response of neutrophils to bacterial activation. Cathelicidin controls the release of inflammatory mediators while increasing antimicrobial activity of neutrophils.
人源抗菌肽 cathelicidin 作为先天免疫系统的效应分子，具有直接的抗菌和免疫调节作用。本研究旨在测试抗菌肽 LL-37 是否调节中性粒细胞对微生物刺激的反应。在与 LL-37 孵育后，用 LPS、金黄色葡萄球菌和铜绿假单胞菌刺激人中性粒细胞，并通过 ELISA 测量细胞因子的释放。LL-37 的孵育显著降低了受刺激的人中性粒细胞中促炎细胞因子的释放。通过发光和流式细胞术方法测定中性粒细胞的 ROS 产生。该肽诱导 ROS 的产生和细菌被中性粒细胞吞噬。用 LPS 和 TNF-α处理从 CRAMP 缺陷型和 WT 动物分离的腹膜鼠中性粒细胞，并通过 ELISA 测量上清液中的细胞因子。通过将来自 CRAMP 敲除和 WT 小鼠的中性粒细胞与细菌孵育，检测中性粒细胞的抗菌活性。与 WT 动物的细胞相比，经细菌刺激后，CRAMP 缺陷型小鼠的中性粒细胞释放出明显更多的 TNF-α，并且抗菌活性降低。总之，LL-37 调节中性粒细胞对细菌激活的反应。抗菌肽在增加中性粒细胞的抗菌活性的同时控制炎症介质的释放。
