The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Experiments with synthetic quartz crystals recently showed that quartz dust is cytotoxic only when the atomic order of the crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz had as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages. To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size differing only in surface properties related to fracturing were prepared and physico-chemically characterized. Synthetic quartz particles were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability and effects on lysosomes were assessed on human PMA-differentiated THP-1 macrophages, upon exposing cells to increasing concentrations of quartz particles (10–250 µg/ml). All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed by incubating macrophages with particles at 4 °C. Membranolysis, but not cytotoxicity, was quenched when fractured quartz was incubated with cells in protein-supplemented medium. We propose that, upon internalization, the phagolysosome environment rapidly removes serum proteins from the quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Our findings indicate that the cytotoxic activity of fractured quartz is elicited by promoting phagolysosomal membrane alteration.

石英的致病性涉及肺泡巨噬细胞中的溶酶体改变。此事件触发了炎症级联反应，可能导致石英诱发的矽肺病并最终导致肺癌。最近使用合成石英晶体进行的实验表明，只有当晶体表面的原子序因破裂而破裂时，石英粉尘才具有细胞毒性。当石英具有未生长的未破裂表面时，未观察到细胞毒性。这些发现对巨噬细胞将颗粒内化后石英表面对吞噬体膜的潜在影响提出了质疑。为了深入了解石英的表面诱导的细胞毒性，制备了可吸入尺寸的，正在生长和破裂的石英颗粒，仅在与破裂有关的表面特性方面不同，并且对其进行了物理化学表征。将合成石英颗粒与众所周知的有毒商业石英粉尘进行了比较。在将细胞暴露于浓度不断增加的石英颗粒（10–250 µg / ml）之后，对红细胞的膜溶解进行了评估，对人PMA分化的THP-1巨噬细胞对石英的吸收，细胞活力以及对溶酶体的影响进行了评估。所有石英样品均被内化，但只有破碎的石英才引起细胞毒性和吞噬体改变。当通过在4°C下孵育巨噬细胞和颗粒来抑制摄取时，这些作用会减弱。当将破碎的石英与补充了蛋白质的培养基中的细胞一起温育时，将膜溶解而不是细胞毒性淬灭。我们建议，在内部化之后，吞噬溶酶体环境会从石英表面快速去除血清蛋白，恢复吞噬体中的石英膜分解活性。我们的发现表明，通过促进吞噬酶体膜的改变可以激发石英碎裂的细胞毒活性。