THP-1 monocytes up-regulate intercellular adhesion molecule 1 in response to pneumolysin from Streptococcus pneumoniae
THP-1 monocytes up-regulate intercellular adhesion molecule 1 in response to pneumolysin from Streptococcus pneumoniae
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DOI：
10.1128/iai.73.10.6493-6498.2005
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发表时间：
2005-10-01
影响因子：
3.1
通讯作者：
McDaniel, LS
中科院分区：
文献类型：
--
作者：
Thornton, J;McDaniel, LS
肺炎球菌溶血素 (PLY) 是肺炎链球菌的主要毒力因子，可引发宿主免疫系统细胞的多种促炎反应。细胞间粘附分子 1 (ICAM-1) 是一种细胞粘附分子，参与白细胞向血管外部位炎症刺激物的运输。在本研究中，我们评估了 PLY 对暴露于肺炎链球菌的 THP-1 单核细胞中 ICAM-1 表达的影响。将细胞暴露于表达 PLY 的肺炎链球菌菌株 WU2 6 小时，与暴露于单独培养基或 Delta PLY1（WU2 的 PLY 阴性同基因突变体）的细胞相比，ICAM-1 信息水平显着升高。与单独暴露于培养基的细胞相比，暴露于纯化重组PLY的细胞也显示出ICAM-1 mRNA的剂量依赖性增加。暴露于含有降低细胞溶解活性的单个氨基酸取代（Trp433-->Phe）的重组 PLY 不会将 ICAM-1 mRNA 增加到野生型 PLY 所见的水平。此外，与分别暴露于单独培养基或其PLY阴性同基因突变体Delta PLY1和Delta PLY2的细胞相比，暴露于野生型菌株WU2或D39的THP-1细胞表面上的ICAM-1增加。这些数据表明，PLY 诱导细胞粘附分子的转录和产生，该细胞粘附分子参与炎症反应，可能在肺炎球菌感染中发挥作用。
Pneumolysin (PLY) is a major virulence factor of Streptococcus pneumoniae that elicits a variety of proinflammatory responses from cells of the host immune system. Intercellular adhesion molecule 1 (ICAM-1) is a cell adhesion molecule involved in leukocyte trafficking toward inflammatory stimuli in extravascular sites. In this study, we evaluated the effect of PLY on expression of ICAM-1 in THP-1 monocytic cells exposed to S. pneumoniae. Exposure of cells to PLY-expressing S. pneumoniae strain WU2 for 6 h led to significantly higher levels of ICAM-1 message than those in cells exposed to either medium alone or Delta PLY1, a PLY-negative isogenic mutant of WU2. Cells exposed to purified recombinant PLY also showed a dose-dependent increase in ICAM-1 mRNA compared to cells exposed to medium alone. Exposure to recombinant PLY containing a single amino acid substitution (Trp433-->Phe) that decreases cytolytic activity did not increase ICAM-1 mRNA to levels seen with wild-type PLY. In addition, THP-1 cells exposed to wild-type strain WU2 or D39 had increased ICAM-1 on their surface compared to cells exposed to medium alone or their PLY-negative isogenic mutants Delta PLY1 and Delta PLY2, respectively. These data indicate that PLY induces transcription and production of a cell adhesion molecule involved in the inflammatory response that may play a role in pneumococcal infection.