Lucarelli Marilena, Gatti Antonietta M, Savarino Graziana, Quattroni Paola, Martinelli Lucia, Monari Emanuela, Boraschi Diana
Unit of Immunobiology, Institute of Biomedical Technologies, CNR, Via Moruzzi 1, I-56124 Pisa, Italy.
Eur Cytokine Netw. 2004 Oct-Dec;15(4):339-46.
Nano-sized particles of ceramic and metallic materials are generated by high-tech industrial activities, and can be generated from worn-out replacement and prosthetic implants. The interaction with the human body of such nanoparticles has been investigated, with a particular emphasis on innate defence mechanisms. Human macrophages (PMA-differentiated myelomonocytic U-937 cells) were exposed in vitro to non-toxic concentrations of TiO(2), SiO(2), ZrO(2), or Co nanoparticles, and their inflammatory response (expression of TLR receptors and co-receptors, and cytokine production) was examined. Expression of TLR receptors was generally unaffected by exposure to the different nanoparticles, except for some notable cases. Exposure to nanoparticles of ZrO(2) (and to a lesser extent TiO(2)), upregulated expression of viral TLR receptors TLR3 and TLR7. Expression of TLR10 was also increased by TiO(2) and ZrO(2) nanoparticles. On the other hand, TLR9 expression was decreased by SiO(2) nano-particles, and expression of the co-receptor CD14 was inhibited by Co nanoparticles. Basal and LPS-induced production of cytokines IL-1beta, TNF-alpha, and IL-1Ra was examined in macrophages exposed to nanoparticles. SiO(2) nanoparticles strongly biased naive macrophages towards inflammation (M1 polarisation), by selectively inducing production of inflammatory cytokines IL-1beta and TNF-alpha. SiO(2) nanoparticles also significantly amplified the inflammatory phenotype of LPS-polarised M1 macrophages. Other ceramic nanoparticles had little influence on cytokine production, either in resting macrophages, or in LPS-activated cells. Generally, Co nanoparticles had an overall pro-inflammatory effect on naive macrophages, by reducing anti-inflammatory IL-1Ra and inducing inflammatory TNF-alpha. However, Co nanoparticles reduced production of IL-1beta and IL-1Ra, but not TNF-alpha, in LPS-polarised M1 macrophages. Thus, exposure to different nanoparticles can modulate, in different ways, the defence/inflammatory capacities of macrophages. A thorough analysis of these biasing effects may shed light on the mechanisms of pathogenesis of several diseases based on dysregulation of the immune response (allergies, autoimmunity, tumours).
高科技工业活动会产生陶瓷和金属材料的纳米级颗粒，并且这些颗粒也可能来自磨损的替换物和假体植入物。人们已经对这类纳米颗粒与人体的相互作用进行了研究，尤其关注先天性防御机制。将人类巨噬细胞（经佛波酯分化的骨髓单核细胞U - 937细胞）在体外暴露于无毒浓度的二氧化钛（TiO₂）、二氧化硅（SiO₂）、氧化锆（ZrO₂）或钴纳米颗粒中，并检测它们的炎症反应（Toll样受体（TLR）及其共受体的表达以及细胞因子的产生）。除了一些显著的情况外，TLR受体的表达通常不受不同纳米颗粒暴露的影响。暴露于氧化锆纳米颗粒（以及程度较轻的二氧化钛纳米颗粒）会上调病毒TLR受体TLR3和TLR7的表达。二氧化钛和氧化锆纳米颗粒也会增加TLR10的表达。另一方面，二氧化硅纳米颗粒会降低TLR9的表达，而钴纳米颗粒会抑制共受体CD14的表达。在暴露于纳米颗粒的巨噬细胞中检测了基础状态下以及脂多糖（LPS）诱导下细胞因子白细胞介素 - 1β（IL - 1β）、肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 1受体拮抗剂（IL - 1Ra）的产生。二氧化硅纳米颗粒通过选择性诱导炎症细胞因子IL - 1β和TNF - α的产生，强烈使未激活的巨噬细胞偏向炎症反应（M1极化）。二氧化硅纳米颗粒还显著增强了LPS极化的M1巨噬细胞的炎症表型。其他陶瓷纳米颗粒对静息巨噬细胞或LPS激活的细胞中的细胞因子产生影响很小。一般来说，钴纳米颗粒通过减少抗炎性的IL - 1Ra并诱导炎性的TNF - α，对未激活的巨噬细胞总体上具有促炎作用。然而，在LPS极化的M1巨噬细胞中，钴纳米颗粒会减少IL - 1β和IL - 1Ra的产生，但不会减少TNF - α的产生。因此，暴露于不同的纳米颗粒可以以不同方式调节巨噬细胞的防御/炎症能力。对这些偏向作用进行全面分析可能会揭示基于免疫反应失调（过敏、自身免疫、肿瘤）的几种疾病的发病机制。
