No e effect o of h histamine o on h human b bronchial e epithelial c cell

Both animal and human studies have suggested that histamine increa- ses airway epithelial cell permeability in vivo. In order to study the effect of hist- amine 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 µM histamine. Cultures were established on microporous membranes of tissue culture cell inserts and used for the assessment of: 1) transepithelial movement of radiolabelled man- nitol (14C-mannitol) and bovine serum albumin (14C-BSA), in the luminal to sero- sal direction and 2) changes in electrical resistance of the cultures. Epithelial cell cultures were also established on plastic coverslips, in order to determine tight junc- tion 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 µM histamine did not signifi- cantly 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 resis- tance 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 lat- ter 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 paracellu- lar bronchial epithelial permeability in vitro.