Trafficking of neutrophils across airway epithelium is dependent upon boththioredoxin- and pertussis toxin-sensitive signaling mechanisms

Leukocyte recruitment from the circulation into the airways is a multi-step process, involving both chemotactic and adhesive mechanisms. Using an in v itro model of leukocyte transepithelial trafficking, we show that movement of human peripheral blood neutrophils (PMN) across airway epithelium in the optimal basolateral-to-apical surface direction is partially blocked by pe rtussis toxin, an inhibitor of G(alpha i)-protein-linked receptors, A neutr alizing monoclonal antibody against interleukin-8 (IL-8; constitutively exp ressed by airway epithelium) did not inhibit PMN transepithelial migration, suggesting that alternative pertussis toxin-sensitive signaling mechanisms are involved. In this process. However, a neutralizing antibody against th ioredoxin, a redox enzyme with pertussis toxin-insensitive chemoattractant activity, did reduce PMN migration across airway epithelium. We conclude th at trafficking of PMN across airway epithelium is mediated by both thioredo xin- and pertussis toxin-sensitive signaling mechanisms that are independen t of IL-8.