An immunohistochemical study of the clearance of apoptotic cellular fragments
An immunohistochemical study of the clearance of apoptotic cellular fragments
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DOI：
10.1007/s00018-002-8513-8
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发表时间：
2002-08-01
影响因子：
8
通讯作者：
Nap, M
中科院分区：
文献类型：
--
作者：
Leers, MPG;Björklund, V;Nap, M
我们研究了人类发育过程中和成人中凋亡小体的分布和命运，使用抗体（M30），该抗体识别细胞角蛋白18的半胱天冬酶裂解在凋亡级联反应早期形成的新表位。在胎仔中，我们发现M30阳性、非吞噬片段在脾脏红髓、皮下和粘膜下血管、肺结节和肾脏肾小球系膜中广泛蓄积。在肝脏中，在窦状隙中的巨噬细胞内发现M30免疫反应性片段。这些片段的数量和免疫染色的强度随着胎龄的增加而增加。在成人中，M30阳性片段在正常组织中几乎检测不到。然而，许多病理情况，包括慢性退行性过程和转移性癌症，与M30阳性片段在脾脏红髓中的积累有关。在肝脏和肾脏中，未检测到碎片。值得注意的是，16名转移性癌症患者中有13名显示脾脏红髓中含有苏木素反应性物质的M30阳性片段明显积聚。在非癌性病例中，仅在94例病例中的9例中观察到此类含DNA片段。结果表明，当凋亡活性高时，如在胎儿的发育期间或在成人的转移和其他病理过程期间，凋亡小体的吞噬清除可能过载。然后这些凋亡片段在脾脏中积累。细胞凋亡片段的视觉检测的结论是反映增加的细胞周转。
We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody (M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus, we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues. However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded. These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect increased cell turnover.