Zhang X M, McDowell E M
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;61(6):375-87. doi: 10.1007/BF02890441.
We showed previously that the proliferation of hamster airway secretory cells decreases during vitamin A deficiency (VAD) but later increases when submucosal inflammation develops (Virchows Arch [B] 59:231-242, 1990). This observation has important biological implications since two morphological extremes (atrophy and quiescence versus hyperplasia and hyperproliferation) are reported in the literature for VAD tracheal epithelium in vivo. In the present study, histological slides of tracheal rings from 35-day-old control and VAD hamsters (Virchows Arch [B] 45:197-219, 1984) were reviewed again. Rings from VAD hamsters were selected based on the absence or presence of a florid submucosal inflammation. Quantitative analyses were made on the cartilaginous part of rings from the anterior third of the trachea. When inflammation was absent, a mucociliary pseudostratified epithelium was, for the most part, maintained. The mitotic rate (MR, 6 h colchicine blockade) of secretory cells was markedly reduced (29-fold) but that of basal cells was not changed significantly. Moreover, cell density was not changed by VAD but ciliated cells and secretory cells were decreased and basal cells were increased, proportionally. We call this "minimal morphological change." Thinning (atrophy) of the minimally changed epithelium was associated with focal cell sloughing. Small scattered foci of epidermoid metaplasia (multiple layers of highly keratinized cells which were extremely flat, so that the epithelium was thin and attenuated) were also seen. We call this "atrophic epidermoid metaplasia." When inflammation was present, hyperplastic changes (stratification and epidermoid metaplasia) predominated and cells were in mitosis at all epithelial levels (low, middle, superficial) except in the most superficial (terminally differentiated) squames. The tracheal epithelium was thickened and hypercellular. The cells were piled up at the stratified lesions, and epithelial height, cell density and epithelial MR were significantly increased compared with the non-inflamed VAD epithelium. The effects of VAD and inflammation on cell proliferation were analyzed further by studying 7 h bromodeoxyuridine (BrdU) labelling patterns of cells in VAD tracheal epithelium, with and without submucosal inflammation. In addition, inflammation was induced in "minimally changed epithelium" by mild mechanical injury. The BrdU labelling patterns confirmed that DNA synthesis by secretory cells is reduced markedly by VAD. However, this suppression is overidden by the influx of inflammatory cells (the nature of the stimulus is unknown). The results indicate that the morphological contrasts (atrophy and hyperplasia) seen in the trachea during VAD in vivo are related to extremes in proliferation rates of tracheal secretory cells, regulated by VAD alone (minimal replication) and by inflammation (maximal replication).
我们之前的研究表明，仓鼠气道分泌细胞的增殖在维生素A缺乏（VAD）期间会减少，但在黏膜下炎症发展时会增加（《Virchows Arch [B]》59:231 - 242, 1990）。这一观察结果具有重要的生物学意义，因为文献报道体内VAD气管上皮存在两种形态学极端情况（萎缩和静止与增生和过度增殖）。在本研究中，我们再次检查了35日龄对照仓鼠和VAD仓鼠（《Virchows Arch [B]》45:197 - 219, 1984）气管环的组织学切片。根据是否存在明显的黏膜下炎症选择VAD仓鼠的气管环。对气管前三分之一处气管环的软骨部分进行了定量分析。当不存在炎症时，大部分情况下会维持假复层纤毛柱状上皮。分泌细胞的有丝分裂率（MR，秋水仙碱阻断6小时）显著降低（29倍），但基底细胞的有丝分裂率没有明显变化。此外，VAD并未改变细胞密度，但纤毛细胞和分泌细胞比例性减少，基底细胞比例性增加。我们将此称为“最小形态学变化”。最小变化上皮的变薄（萎缩）与局灶性细胞脱落有关。还可见到小的散在性表皮样化生灶（多层高度角化的细胞，极其扁平，因此上皮变薄且变细）。我们将此称为“萎缩性表皮样化生”。当存在炎症时，增生性变化（分层和表皮样化生）占主导，除最表层（终末分化）的鳞状细胞外，所有上皮层次（低、中、表层）的细胞都处于有丝分裂状态。气管上皮增厚且细胞增多。细胞在分层病变处堆积，与未发炎的VAD上皮相比，上皮高度、细胞密度和上皮MR显著增加。通过研究VAD气管上皮中有无黏膜下炎症时细胞的7小时溴脱氧尿苷（BrdU）标记模式，进一步分析了VAD和炎症对细胞增殖的影响。此外，通过轻度机械损伤在“最小变化上皮”中诱导炎症。BrdU标记模式证实，VAD显著降低了分泌细胞的DNA合成。然而，这种抑制被炎症细胞的涌入所抵消（刺激的性质未知）。结果表明，体内VAD期间气管中所见的形态学对比（萎缩和增生）与气管分泌细胞增殖率的极端情况有关，单独由VAD调节（最小复制）和由炎症调节（最大复制）。
