Hypersecretion of mucin in response to inflammatory mediators by guinea pig tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide synthase

Am J Respir Cell Mol Biol. 1995 Nov;13(5):526-30. doi: 10.1165/ajrcmb.13.5.7576687.


Primary cultures of guinea pig tracheal epithelial cells in air/liquid interface were exposed to one of four agents associated with airway inflammation: the peptide histamine (100 microM), the lipid mediator platelet-activating factor (1 microM), the cytokine tumor necrosis factor-alpha (15 ng/ml; specific activity 2.86 x 10(7) U/mg), or enzymatically generated reactive oxygen species (purine [500 microM]+xanthine oxidase [20 mU/ml]). Effects of each of these substances on release of mucin by guinea pig tracheal epithelial (GPTE) cells were measured using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Each secretagogue significantly enhanced release of mucin, but the stimulatory effect of each was inhibited by pre-(+)co-incubation of the cells with the competitive inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMA), but not by NG-monomethyl-D-arginine (D-NMA), the inactive stereoisomer that does not inhibit nitric oxide synthase. Neither L-NMA nor D-NMA affected mucin secretion by themselves. The results suggest that each of these inflammation-associated mediators provokes airway epithelial mucin secretion via a mechanism involving intracellular production of nitric oxide (NO) as a critical signaling molecule.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Guinea Pigs
  • Histamine / pharmacology
  • Inflammation Mediators / pharmacology*
  • Mucins / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Platelet Activating Factor / drug effects
  • Secretory Rate / drug effects
  • Superoxides / metabolism
  • Trachea / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • omega-N-Methylarginine


  • Enzyme Inhibitors
  • Inflammation Mediators
  • Mucins
  • Platelet Activating Factor
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • omega-N-Methylarginine
  • Histamine
  • Arginine
  • Nitric Oxide Synthase