Myklebust R, Mayhew T M
Department of Electron Microscopy, Faculty of Medicine, University of Tromso, Norway.
Cell Tissue Res. 1998 Mar;291(3):513-23. doi: 10.1007/s004410051021.
Ultrastructural studies were conducted on mechanisms of epithelial cell loss in the small intestine of seal and reindeer. Mechanisms maintaining epithelial integrity were distinguished from those that did not and the non-epithelial cell types involved were identified. Three types of cell extrusion were noted. In two, tight junctional integrity was preserved and anucleate apical cell fragments (rather than complete cells) were lost into the lumen. In reindeer (type 1), this involved creating large intercellular spaces extending from the preserved apical cap to the lamina propria and containing enterocyte debris probably phagocytosed by subepithelial macrophages. A variant of this process (type 2) involved the gradual shrinkage of individual cells, which became more electron-dense, and the in situ degeneration of their nucleated subapical portions. Degenerated cell fragments and membrane whorls were confined to narrow intercellular spaces between approximating adjacent healthy enterocytes. The mechanism of removal of these fragments was unclear. In both cases, the proximity of intraepithelial lymphocytes suggested that they were involved in cell targetting and killing. Evidence of apoptotic nuclei was not found but nucleated cell fragments could have been washed out of the lumen during tissue preparation. Type 2 cell loss was seen in both species, as was another mechanism (type 3) reminiscent of necrosis. In contrast to other mechanisms, this was accompanied by breaks in epithelial continuity following gradual loss of cell electron density and total or subtotal degradation of organelles and membranes. In seal, this terminated in the loss of an abnormal cell apex and exposure of the contents of the cell remnant to the lumen. In reindeer, all the cell remnants may have been extruded before total membrane degeneration but, in both species, the otherwise tight epithelial barrier was clearly breached. Again, intraepithelial lymphocytes were associated with sites of necrosis. These findings provide evidence for further species differences in mechanisms of epithelial cell extrusion and suggest that necrotic cell loss may be more common than previously admitted.
对海豹和驯鹿小肠上皮细胞丢失机制进行了超微结构研究。区分了维持上皮完整性的机制与未维持上皮完整性的机制，并确定了所涉及的非上皮细胞类型。观察到三种细胞挤出类型。其中两种类型中，紧密连接完整性得以保留，无核顶端细胞碎片（而非完整细胞）丢失到肠腔中。在驯鹿中（类型1），这涉及形成从保留的顶端帽延伸至固有层的大细胞间隙，其中含有可能被上皮下巨噬细胞吞噬的肠上皮细胞碎片。该过程的一种变体（类型2）涉及单个细胞逐渐收缩，细胞变得电子密度更高，其有核的顶端下部分原位退化。退化的细胞碎片和膜性涡旋局限于相邻健康肠上皮细胞之间狭窄的细胞间隙。这些碎片的清除机制尚不清楚。在这两种情况下，上皮内淋巴细胞的存在表明它们参与了细胞靶向和杀伤。未发现凋亡核的证据，但有核细胞碎片可能在组织制备过程中被冲出肠腔。两种物种均可见类型2细胞丢失，还有另一种类似坏死的机制（类型3）。与其他机制不同的是，这种机制伴随着上皮连续性的中断，随后细胞电子密度逐渐降低，细胞器和膜完全或部分降解。在海豹中，这导致异常细胞顶端丢失，细胞残余物内容物暴露于肠腔。在驯鹿中，所有细胞残余物可能在膜完全退化之前就已挤出，但在这两种物种中，原本紧密的上皮屏障明显被破坏。同样，上皮内淋巴细胞与坏死部位相关。这些发现为上皮细胞挤出机制的进一步物种差异提供了证据，并表明坏死性细胞丢失可能比之前认为的更为常见。
