title: Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms.
abstract: Leukocyte recruitment from the circulation into the airways is a multi-step process, involving both chemotactic and adhesive mechanisms. Using an in vitro 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 pertussis toxin, an inhibitor of G(alphai)-protein-linked receptors. A neutralizing monoclonal antibody against interleukin-8 (IL-8; constitutively expressed 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 thioredoxin, a redox enzyme with pertussis toxin-insensitive chemoattractant activity, did reduce PMN migration across airway epithelium. We conclude that trafficking of PMN across airway epithelium is mediated by both thioredoxin- and pertussis toxin-sensitive signaling mechanisms that are independent of IL-8.
authors.affiliation: The Center for Comparative Respiratory Biology and Medicine and Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616, USA. lmiller@ucdavis.edu
authors.forename: L A
authors.initials: LA
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Usachenko
authors.forename: R J
authors.initials: RJ
authors.lastname: McDonald
authors.forename: D M
authors.initials: DM
authors.lastname: Hyde
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D037342:Pertussis Toxin; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013879:Thioredoxins / Q000378:metabolism / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D010566:Virulence Factors, Bordetella; D013879:Thioredoxins; D037342:Pertussis Toxin