Fine Particles That Adsorb Lipopolysaccharide Via Bridging Calcium Cations May Mimic Bacterial Pathogenicity Towards Cells
Fine Particles That Adsorb Lipopolysaccharide Via Bridging Calcium Cations May Mimic Bacterial Pathogenicity Towards Cells
复制标题
DOI：
10.3181/00379727-207-2320107
复制
发表时间：
2007-01
影响因子：
3.2
通讯作者：
P. Ashwood;R. Thompson;J. Powell
中科院分区：
文献类型：
--
作者：
P. Ashwood;R. Thompson;J. Powell
细颗粒（直径102- 103nm）在获得性免疫反应中是潜在的强效佐剂，但对它们与病原体相关分子模式（PAMPs）的相互作用以及对先天免疫的影响知之甚少。本研究表明，200纳米大小的食品级二氧化钛可将脂多糖（LPS）与桥接钙离子结合，该复合物可在人单核吞噬细胞中诱导显著的促炎信号传导。特别是，caspase -1依赖性白介素-1β (IL-1β)的分泌水平远远大于单个成分的总和，并且没有同时分泌白介素-1受体拮抗剂或转化生长因子-β1 （TGF-β1）等调节细胞因子。其次，偶联物诱导凋亡样细胞死亡。这些反应被吞噬作用和清道夫受体摄取的阻断所抑制。特异性的caspase 1促进IL-1β分泌和吞噬后的细胞凋亡是细胞对某些侵袭性肠道病原体反应的特征，因此这些事件的诱导可能被细颗粒lps偶联物模拟。PAMPs对摄入、吸入或“磨损”细颗粒物的无意吸附为细颗粒物的促炎性质提供了进一步的潜在机制。
Fine particles (102- to 103-nm diameter) are potentially potent adjuvants in acquired immune responses but little is known about their interaction with pathogen-associated molecular patterns (PAMPs) and impact upon innate immunity. Here we show that 200-nm–sized, food-grade titanium dioxide avidly binds lipopolysaccharide (LPS) with bridging calcium cations, and the complex induces marked proinflammatory signalling in primary human mononuclear phagocytes. In particular, caspase 1-dependent interleukin-1β (IL-1β) secretion was induced at levels far greater than for the sum of the individual components, and without concomitant secretion of modulatory cytokines such as interleukin-1 receptor antagonist or transforming growth factor-β1 (TGF-β1). Secondly, the conjugate induced apoptotic-like cell death. These responses were inhibited by blockade of both phagocytosis and scavenger receptor uptake. Specific caspase 1–facilitated IL-1β secretion and apoptosis following phagocytosis are features of cellular responses to certain invasive, enteric pathogens, and hence induction of these events may be mimicked by fine particle–LPS conjugates. The inadvertent adsorption of PAMPs to ingested, inhaled, or “wear” fine particulate matter provides a further potential mechanism for the proinflammatory nature of fine particles.