Inhibition of mucin release from airway goblet cells by polycationic peptides

In the present study, we investigated whether polycationic peptides affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled with [H-3 ]glucosamine for 24 h and chased for 30 min in the presence of varying conc entrations of either poly-L-arginine (PLA) or poly-L-lysine (PLL) to assess the effects on [H-3]mucin release. Possible cytotoxicity by the polycation s was assessed by measuring lactate dehydrogenase release, Cr-51 release, a nd cell exfoliation. The results were as follows: 1) both PLA and PLL inhib ited mucin release in a dose-dependent fashion; 2) there was no significant difference in either lactate dehydrogenase release, Cr-51 release, or the number of floating cells between control and treatment groups; 3) the effec ts of both PLA and PLL on mucin release were completely blocked by neutrali zing the positive charges either by pretreatment with heparin or by N-acety lation of the polycations; and 4) both PLA and PLL completely masked the st imulatory effect of ATP on mucin release. We conclude that these polycation ic peptides can inhibit mucin release from airway goblet cells without any apparent cytotoxicity, and the inhibitory effect seems to be attributable t o their positive charges. These are the first nonsteroidal agents, to the b est of our knowledge, that have been shown to inhibit mucin release from ai rway goblet cells.