Mathiak Guenther, Kabir Koroush, Grass Guido, Keller Hendrik, Steinringer Eva, Minor Thomas, Rangger Christoph, Neville Lewis F
Department of Trauma Surgery, University Hospital of Bonn Medical School, Bonn, Germany.
Int J Mol Med. 2003 Jan;11(1):41-4.
The stimulatory effects of different purified lipopolysaccharide (LPS) preparations from E. coli, S. typhosa, P. aeruginosa, and K. pneumoniae on cytokine and chemokine production were measured in whole blood assays by ELISA. Incubation of 0.5 ml whole blood with 10 ng/ml E. coli and S. typhosa resulted in a time-dependent production of TNF-alpha, IL-1beta, IFN-gamma, IL-10 and MCP-1. K. pneumoniae, however, showed preferential effects on IL-1beta, IL-10 and MCP-1 production with less potent effects on TNF-alpha and IFN-gamma. LPS derived from P. aeruginosa showed a similar potency to other LPS preparations on MCP-1 production, yet completely failed to elicit the production of other cytokines. To further investigate potencies of the different LPS preparations, mediator production was determined following stimulation with agonist concentrations of 0.1 ng and 1000 ng per ml over a 24 h time period. Dose-response curves were obtained with LPS derived from E. coli, S. typhosa and K. pneumoniae on all mediators apart from IL-1beta and MCP-1. Most strikingly though, was the ability of LPS derived from P. aeruginosa to selectively elicit a significant dose-response effect on MCP-1 production, despite its very weak stimulatory effects on all other cytokines. These data imply that the bacterial origin of different LPS preparations can exhibit disparate effects on inflammatory mediator production. Furthermore, the potent, selective dose-response effect of P. aeruginosa LPS on MCP-1 production could help to explain the preponderance of a relentless inflammatory cellular infiltrate in diseases such as cystic fibrosis (CF).
通过酶联免疫吸附测定（ELISA）全血检测法，测定了来自大肠杆菌、伤寒沙门氏菌、铜绿假单胞菌和肺炎克雷伯菌的不同纯化脂多糖（LPS）制剂对细胞因子和趋化因子产生的刺激作用。用10纳克/毫升的大肠杆菌和伤寒沙门氏菌与0.5毫升全血孵育，导致肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、白细胞介素-10（IL-10）和单核细胞趋化蛋白-1（MCP-1）呈时间依赖性产生。然而，肺炎克雷伯菌对IL-1β、IL-10和MCP-1的产生有优先作用，而对TNF-α和IFN-γ的作用较弱。来自铜绿假单胞菌的LPS在MCP-1产生方面显示出与其他LPS制剂相似的效力，但完全未能引发其他细胞因子的产生。为了进一步研究不同LPS制剂的效力，在24小时时间段内用每毫升0.1纳克和1000纳克的激动剂浓度刺激后测定介质产生。除了IL-1β和MCP-1外，用来自大肠杆菌、伤寒沙门氏菌和肺炎克雷伯菌的LPS获得了所有介质的剂量反应曲线。不过，最引人注目的是，尽管铜绿假单胞菌LPS对所有其他细胞因子的刺激作用非常微弱，但它有能力选择性地引发对MCP-1产生的显著剂量反应效应。这些数据表明，不同LPS制剂的细菌来源对炎症介质产生可能表现出不同的影响。此外，铜绿假单胞菌LPS对MCP-1产生的强大、选择性剂量反应效应有助于解释诸如囊性纤维化（CF）等疾病中持续存在的炎症细胞浸润的优势。
