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 effect of histamine on paracellular epithelial permeability and tight junctional integrity, we have cultured human bronchial epithelial cells to confluency and investigated the effect of topically applied 0.1-20.0 microM histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transepithelial movement of radiolabelled mannitol (14C-mannitol) and bovine serum albumin (14C-BSA), in the luminal to serosal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cultures were also established on plastic coverslips, in order to determine tight junction morphology by freeze-fracture electron microscopy, and to assess junctional integrity by lanthanum penetration, using thin sections. Compared with untreated control cultures, 0.1-10 microM histamine did not significantly alter the movement of either 14C-mannitol or 14C-BSA across the epithelial cultures at any time during incubation, but caused an increase in the electrical resistance of the cultures, which was maximal by 6 h of incubation. The morphology of the tight junctions revealed by freeze-fracture and junctional integrity (the latter determined by the degree of lanthanum penetration) were similar in untreated control cultures and cultures incubated with histamine. These studies indicate that histamine does not have a direct effect on paracellular bronchial epithelial permeability in vitro.