Deininger Susanne, Traub Stephanie, Aichele Diana, Rupp Tamara, Baris Teodora, Möller Heiko M, Hartung Thomas, von Aulock Sonja
Biochemical Pharmacology, University of Konstanz, Universitaetsstr. 10, 78464 Konstanz, Germany.
Immunobiology. 2008;213(6):519-29. doi: 10.1016/j.imbio.2008.01.001. Epub 2008 Feb 14.
Lipoteichoic acid (LTA) is a major immunostimulatory molecule in the cell wall of Gram-positive bacteria. Adhesion of LTA to a polystyrene surface drastically increased its immunostimulatory potency in human whole blood in comparison to soluble LTA, although only 1% of the LTA had bound, as determined using rhodamine-labelled LTA. The release of the proinflammatory cytokines IL-1beta, TNF and IL-6 and the chemokines IL-8 and G-CSF was increased 2- to 10-fold, but IL-10 release was unaltered. This presentation effect was not shared by lipopolysaccharide (LPS) or other toll-like receptor 2 agonists and was less pronounced in polypropylene vessels. LTA did not induce cytokine release in silicone-coated borosilicate vessels, but covalent coupling of LTA to polystyrene beads restored cytokine induction in these vessels, indicating that presentation of LTA on a surface is in fact essential for its immunostimulatory potency. This novel aspect of presentation as a factor in the recognition of LTA may reflect the physiological situation in the bacterial cell wall, where LTA is anchored in the bacterial membrane and projects through the peptidoglycan. In practical terms, contamination of medical devices with components of Gram-positive bacteria may pose an underestimated inflammatory risk.
脂磷壁酸(LTA)是革兰氏阳性菌细胞壁中的一种主要免疫刺激分子。与可溶性LTA相比,LTA与聚苯乙烯表面的黏附显著增强了其在人全血中的免疫刺激效力,尽管使用罗丹明标记的LTA测定发现只有1%的LTA发生了结合。促炎细胞因子IL-1β、TNF和IL-6以及趋化因子IL-8和G-CSF的释放增加了2至10倍,但IL-10的释放未改变。脂多糖(LPS)或其他Toll样受体2激动剂不具有这种呈递效应,且在聚丙烯容器中这种效应不太明显。LTA在硅酮涂层硼硅酸盐容器中不会诱导细胞因子释放,但LTA与聚苯乙烯珠的共价偶联恢复了这些容器中的细胞因子诱导,表明LTA在表面的呈递实际上对其免疫刺激效力至关重要。作为LTA识别因素的这种呈递新特性可能反映了细菌细胞壁中的生理情况,其中LTA锚定在细菌膜中并穿过肽聚糖突出。实际上,医疗器械被革兰氏阳性菌成分污染可能带来被低估的炎症风险。