Shirahama T, Cohen A S
Am J Pathol. 1974 Sep;76(3):501-20.
To obtain direct evidence for the mechanism involved in gouty inflammation, human leukocytes were incubated with synthetic monosodium urate microcrystals. To trace the phago(lyso)somal contents, colloidal carbon, ferritin, Thorotrast(R) or horseradish peroxidase was added to the incubation medium, or acid phosphatase activity was localized cytochemically. The interaction was analyzed in time sequence by electron microscopy. By 5 minutes' incubation, urate crystals and tracers had appeared in the single membrane-bounded vacuoles of leukocytes. After 30 minutes' incubation, the vacuoles containing the urate crystals and the tracers were found in more than 50% of the leukocyte population. The phago(lyso)somal membrane was occasionally discontinuous, and the tracers were found in the free cytoplasm near the membrane opening as well. After 60 minutes' or more incubation, the phago(lyso)somal changes and the cytoplasmic localization of the tracers were common, and many cells showed signs of degeneration. Urate crystals mixed in cell debris were often found to be ingested by other leukocytes. These results have been interpreted as follows. Monosodium urate crystals are avidly phagocytized. The urate crystal-containing phagosomes eventually become phagolysosomes. The phagolysosomal membrane is damaged and the contents leak out into the cytoplasm. The leakage of the hydrolases initiates the host cell injury. The urate crystals released by cell disruption are again phagocytized by other cells and the series of events are repeated.
为了获得痛风性炎症相关机制的直接证据，将人白细胞与合成尿酸钠微晶一起孵育。为了追踪吞噬（溶酶）体的内容物，将胶体碳、铁蛋白、钍造影剂或辣根过氧化物酶添加到孵育培养基中，或者通过细胞化学方法定位酸性磷酸酶活性。通过电子显微镜按时间顺序分析这种相互作用。孵育5分钟后，尿酸盐晶体和示踪剂出现在白细胞的单膜包被空泡中。孵育30分钟后，超过50%的白细胞群体中发现含有尿酸盐晶体和示踪剂的空泡。吞噬（溶酶）体膜偶尔会不连续，并且在膜开口附近的游离细胞质中也发现了示踪剂。孵育60分钟或更长时间后，吞噬（溶酶）体变化和示踪剂在细胞质中的定位很常见，许多细胞显示出退化迹象。常常发现混在细胞碎片中的尿酸盐晶体被其他白细胞吞噬。这些结果被解释如下。尿酸钠晶体被大量吞噬。含有尿酸盐晶体的吞噬体最终变成吞噬溶酶体。吞噬溶酶体膜受损，内容物泄漏到细胞质中。水解酶的泄漏引发宿主细胞损伤。细胞破裂释放的尿酸盐晶体再次被其他细胞吞噬，这一系列事件不断重复。
