NO EFFECT OF HISTAMINE ON HUMAN BRONCHIAL EPITHELIAL-CELL PERMEABILITY AND TIGHT JUNCTIONAL INTEGRITY IN-VITRO

Both animal and human studies have suggested that histamine increases airway epithelial cell permeability in vivo. In order to study the eff ect of histamine on paracellular epithelial permeability and tight jun ctional integrity, we have cultured human bronchial epithelial cells t o confluency and investigated the effect of topically applied 0.1-20.0 mu M histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transe pithelial movement of radiolabelled mannitol (C-14-mannitol) and bovin e serum albumin (C-14-BSA), in the luminal to serosal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cul tures were also established on plastic coverslips, in order to determi ne tight-junction morphology by freeze-fracture electron microscopy, a nd to assess junctional integrity by lanthanum penetration, using thin sections. Compared with untreated control cultures, 0.1-10 mu M hista mine did not significantly alter the movement of either C-14-mannitol or C-14-BSA across the epithelial cultures at any time during incubati on, but caused an increase in the electrical resistance of the culture s, which was maximal by 6 h of incubation. The morphology of the tight junctions revealed by freeze-fracture and junctional integrity (the l atter determined by the degree of lanthanum penetration) were similar in untreated control cultures and cultures incubated with histamine. T hese studies indicate that histamine does not have a direct effect on paracellular bronchial epithelial permeability in vitro.