群体感应淬灭抗体RS2-1G9可保护巨噬细胞免受铜绿假单胞菌群体感应信号分子N-3-氧代十二烷酰高丝氨酸内酯的细胞毒性作用。
The quorum quenching antibody RS2-1G9 protects macrophages from the cytotoxic effects of the Pseudomonas aeruginosa quorum sensing signalling molecule N-3-oxo-dodecanoyl-homoserine lactone.
作者信息
Kaufmann Gunnar F, Park Junguk, Mee Jenny M, Ulevitch Richard J, Janda Kim D
机构信息
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Mol Immunol. 2008 May;45(9):2710-4. doi: 10.1016/j.molimm.2008.01.010. Epub 2008 Mar 4.
Abstract
The Gram-negative bacterium Pseudomonas aeruginosa, an opportunistic human pathogen, uses acyl-homoserine lactone-based quorum sensing systems to control its pathogenicity. One of its quorum sensing factors, N-3-oxo-dodecanoyl-homoserine lactone, has been shown not only to mediate bacterial quorum sensing but also to exert cytotoxic effects on mammalian cells. The monoclonal antibody RS2-1G9 generated against a 3-oxo-dodecanoyl-homoserine lactone analogue hapten was able to protect murine bone marrow-derived macrophages from the cytotoxic effects and also prevented the activation of the mitogen-activated protein kinase p38. These data demonstrate that an immunopharmacotherapeutic approach to combat P. aeruginosa infections might be a viable therapeutic option as the monoclonal antibody RS2-1G9 can readily sequester bacterial N-3-oxo-dodecanoyl-homoserine lactone molecules, thus interfering with their biological effects in prokaryotic and eukaryotic systems.
摘要
革兰氏阴性菌铜绿假单胞菌是一种机会性人类病原体，它利用基于酰基高丝氨酸内酯的群体感应系统来控制其致病性。其群体感应因子之一N-3-氧代十二烷酰高丝氨酸内酯不仅已被证明可介导细菌群体感应，还对哺乳动物细胞具有细胞毒性作用。针对3-氧代十二烷酰高丝氨酸内酯类似物半抗原产生的单克隆抗体RS2-1G9能够保护小鼠骨髓来源的巨噬细胞免受细胞毒性作用，还能阻止丝裂原活化蛋白激酶p38的激活。这些数据表明，对抗铜绿假单胞菌感染的免疫药物治疗方法可能是一种可行的治疗选择，因为单克隆抗体RS2-1G9能够轻易地螯合细菌的N-3-氧代十二烷酰高丝氨酸内酯分子，从而干扰它们在原核和真核系统中的生物学效应。
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