Neutrophil transmigration across human airway epithelial monolayers - Mechanisms and dependence on electrical resistance

To examine neutrophil transepithelial migration in the basolateral-to-lumin al direction, bronchial epithelial cells (16HBE) were grown at an air-mediu m interface on the lower face of permeable supports, and resistance across each membrane was recorded before measuring neutrophil transmigration over 2 h. Subconfluent monolayers (resistance < 250 Omega) permitted high sponta neous migration of neutrophils (7.4 +/- 1%), which was further enhanced (29 .7 +/- 3%) in response to interleukin (IL)-8 (100 ng/ml). Confluent monolay ers (250 to 700 Omega) showed low spontaneous migration (2 +/- 0.5%) but re sponded markedly to IL-8 (12.4 +/- 1.3%). Left in culture, 16HBE resistance s continued to increase and were associated with minimal spontaneous migrat ion (( 0.5%) or responses to IL-8. Using cells in the 250 to 700 hi range, neutrophil migration to IL-8 was dose-dependent and was enhanced when epith elial cells were incubated with a combination of tumor necrosis factor-alph a and interferon-gamma, Neutrophil migration was stimulus-specific and was reduced by preincubation of epithelial cells with a F(ab')(2) anti-intercel lular adhesion molecule (ICAM)-1, or by preincubation of neutrophils with a nti-CD18, anti-CD11a, anti-CD11b, or anti-CD11c, but not by anti-CD11d, ind icating a role for beta(2)-integrin-ICAM-1 interaction in the migration pro cess.