Lou Y P, Takeyama K, Grattan K M, Lausier J A, Ueki I F, Agustí C, Nadel J A
Cardiovascular Research Institute and Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1927-34. doi: 10.1164/ajrccm.157.6.9709113.
In patients dying from asthma, extensive mucous plugging occurs in the airways, associated with goblet cell hyperplasia. In this study, we examined the hypothesis that platelet-activating factor (PAF) induces goblet cell hyperplasia and mucin gene expression. After instilling PAF into the airways of guinea pigs and rats, we stained airway goblet cells with Alcian blue/periodic acid-Schiff and determined the number of goblet cells and percentage of stained area within the epithelium. In guinea pigs, one instillation of PAF (10(-)5 M, 100 microl) increased the goblet cell-stained area time-dependently, beginning at 24 h, maximum at 72 h. PAF also caused tracheal recruitment of eosinophils by 24 h, maximum at 48 h. In rats, which have few goblet cells in airways, PAF (3 instillations, 10(-)5 M, 200 microl) caused striking goblet cell hyperplasia, greatest in peripheral airways. Tumor necrosis factor alpha (TNFalpha) alone had no significant effect on goblet cells, but together with PAF, it caused exaggerated goblet cell hyperplasia. In rat tracheas studied by in situ hybridization, PAF induced mucin MUC5 gene expression in epithelial cells that stained for mucosubstances. In summary, PAF induces goblet cell hyperplasia and TNFalpha potentiates this effect.
在死于哮喘的患者中，气道内会出现广泛的黏液阻塞，这与杯状细胞增生有关。在本研究中，我们检验了血小板活化因子（PAF）诱导杯状细胞增生和黏蛋白基因表达的假说。将PAF滴入豚鼠和大鼠气道后，我们用阿尔辛蓝/过碘酸希夫试剂对气道杯状细胞进行染色，并确定杯状细胞数量以及上皮内染色区域的百分比。在豚鼠中，单次滴入PAF（10⁻⁵ M，100微升）可使杯状细胞染色区域随时间增加，从24小时开始，72小时达到最大值。PAF还在24小时时引起气管嗜酸性粒细胞募集，48小时时达到最大值。在气道杯状细胞较少的大鼠中，PAF（滴入3次，10⁻⁵ M，200微升）引起显著的杯状细胞增生，在外周气道最为明显。单独的肿瘤坏死因子α（TNFα）对杯状细胞无显著影响，但与PAF共同作用时，会导致杯状细胞增生加剧。在通过原位杂交研究的大鼠气管中，PAF诱导了对黏液物质染色的上皮细胞中黏蛋白MUC5基因的表达。总之，PAF诱导杯状细胞增生，TNFα增强了这种作用。
