Am. J. Respir. Crit. Care Med., Volume 157, Number 6, June 1998, 1927-1934

Platelet-activating Factor Induces Goblet Cell Hyperplasia and Mucin Gene Expression in Airways

YA-PING LOU, KIYOSHI TAKEYAMA, KATHLEEN M. GRATTAN, JAMES A. LAUSIER, IRIS F. UEKI, CARLOS AGUSTÍ, and JAY A. NADEL

Cardiovascular Research Institute and Department of Medicine, University of California San Francisco, San Francisco, California

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 (10⁵ M, 100 µl) 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, 10⁵ M, 200 µl) caused striking goblet cell hyperplasia, greatest in peripheral airways. Tumor necrosis factor alpha (TNF) 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 TNF potentiates this effect.

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