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首页> 外文期刊>Infection and immunity >Potent CD14-mediated signalling of human leukocytes by Escherichia coli can be mediated by interaction of whole bacteria and host cells without extensive prior release of endotoxin.
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Potent CD14-mediated signalling of human leukocytes by Escherichia coli can be mediated by interaction of whole bacteria and host cells without extensive prior release of endotoxin.

机译:大肠杆菌的强力CD14介导人白细胞信号转导可以通过整个细菌与宿主细胞的相互作用来介导,而无需事先大量释放内毒素。

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How invading microorganisms are detected by the host has not been well defined. We have compared the abilities of Escherichia coli and lipopolysaccharides (LPS) purified from these bacteria to prime isolated neutrophils for phorbol myristate acetate-stimulated arachidonate release, to trigger respiratory burst in 1% blood, and to increase steady-state levels of tumor necrosis factor alpha mRNA in whole blood. In all three assays, bacteria were > or = 10-fold more potent than equivalent amounts of LPS and could trigger maximal cellular responses at ratios as low as one bacterium per 20 to 200 leukocytes. Both E. coli and LPS-triggered responses were enhanced by LPS-binding protein and inhibited by an anti-CD14 monoclonal antibody and the bactericidal/permeability-increasing protein (BPI). However, whereas O polysaccharide did not affect the potency of isolated LPS, intact E. coli carrying long-chain LPS (O111:B4) was less potent than rough E. coli (J5). Furthermore, material collected by filtration or centrifugation of bacteria incubated under conditions used to trigger arachidonate release or chemiluminescence was 5- or 30-fold less active, respectively, than whole bacterial suspensions. Extracellular BPI (not bound to bacteria) inhibited bacterial signalling, but BPI bound to bacteria was much more potent. Taken together, these findings indicate that E. coli cells can strongly signal their presence to human leukocytes not only by shedding LPS into surrounding fluids but also by exposing endotoxin at or near their surface during direct interaction with host cells.
机译:宿主如何检测入侵微生物尚未明确。我们已经比较了大肠杆菌和从这些细菌中纯化的脂多糖(LPS)对佛波肉豆蔻酸酯乙酸酯刺激的花生四烯酸酯释放,引发1%血液中的呼吸爆发以及增加稳态的肿瘤坏死因子水平的分离中性粒细胞的能力。全血中的αmRNA。在所有三种测定中,细菌的效力比同等量的LPS强>或= 10倍,并且可以以每20到200个白细胞一种细菌的比率触发最大的细胞反应。 LPS结合蛋白可增强大肠杆菌和LPS触发的响应,而抗CD14单克隆抗体和杀菌/通透性增强蛋白(BPI)则可抑制这种反应。但是,虽然O多糖不会影响分离的LPS的效力,但完整的带有长链LPS的大肠杆菌(O111:B4)的效力不如粗糙的大肠杆菌(J5)。此外,通过过滤或离心细菌而收集的材料在用于触发花生四烯酸盐释放或化学发光的条件下孵育的活性分别比整个细菌悬浮液低5或30倍。细胞外BPI(不与细菌结合)抑制细菌信号传导,但与细菌结合的BPI更有效。综上所述,这些发现表明,大肠杆菌细胞不仅可以通过将LPS释放到周围的液体中,而且还可以在与宿主细胞直接相互作用的过程中在其表面或附近暴露内毒素,从而向人白细胞强烈表达它们的存在。

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