Shimizu T, Takahashi Y, Kawaguchi S, Sakakura Y
Department of Otorhinolaryngology, Mie University School of Medicine, Tsu, Mie, Japan.
Am J Respir Crit Care Med. 1996 Apr;153(4 Pt 1):1412-8. doi: 10.1164/ajrccm.153.4.8616574.
To elucidate the mechanisms of epithelial mucus hypersecretion in upper respiratory airway inflammation, we produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by intranasal instillation of endotoxin. Significant increase of hypertrophic goblet cells was induced in the septal epithelium transversely sectioned at the level of incisive papilla at 24 h after the intranasal instillation of 0.1 mg of endotoxin. This change was completed after 3 d of endotoxin instillations and recovered by normal epithelium 7 d after the last instillation. Total cell number and the number of basal and ciliated cells counted over 2 mm of basal lamina did not change; however, the number of goblet cells increased and that of nongranulated secretory cells decreased time-dependently after endotoxin instillations. Mitotic rates examined after a 6-h colchicine metaphase blockade were very low at any time point studied, and cell division did not play a major role in this process. These results indicate that endotoxin induces hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium rather than a hyperplastic change, and this metaplasia is produced by direct conversion of nongranulated secretory cells into the goblet cells. Histochemical examination of this epithelium revealed that most of the mucus produced by these goblet cells was sulfomucin. Intraperitoneal injection of antirat neutrophil antiserum or cyclophosphamide depleted circulating blood neutrophils. Endotoxin-induced changes of goblet cells were significantly inhibited in these neutrophil-depleted rats, and intranasal instillation of elastase also induced hypertrophic and metaplastic changes of goblet cells.
为阐明上呼吸道炎症中上皮黏液分泌过多的机制，我们通过鼻内滴注内毒素使大鼠鼻呼吸上皮杯状细胞发生肥大和化生改变。在鼻内滴注0.1mg内毒素后24小时，在切牙乳头水平横切的鼻中隔上皮中诱导出肥大杯状细胞显著增加。这种变化在内毒素滴注3天后完成，并在最后一次滴注7天后恢复为正常上皮。在2mm基膜上计数的总细胞数以及基底细胞和纤毛细胞数没有变化；然而，内毒素滴注后杯状细胞数量增加，非颗粒分泌细胞数量随时间减少。在秋水仙碱中期阻断6小时后检测的有丝分裂率在任何研究时间点都非常低，细胞分裂在这个过程中不发挥主要作用。这些结果表明，内毒素诱导大鼠鼻上皮杯状细胞发生肥大和化生改变而非增生改变，这种化生是由非颗粒分泌细胞直接转化为杯状细胞产生的。对该上皮的组织化学检查显示，这些杯状细胞产生的大部分黏液是硫黏蛋白。腹腔注射抗大鼠中性粒细胞抗血清或环磷酰胺可使循环血液中的中性粒细胞减少。在这些中性粒细胞减少的大鼠中，内毒素诱导的杯状细胞变化受到显著抑制，鼻内滴注弹性蛋白酶也可诱导杯状细胞发生肥大和化生改变。
