Activation of Extracellular Regulated Kinases Is Required for the Increase in Airway Epithelial Permeability during Leukocyte Transmigration

Vladimir B. Serikov, Hyon Choi, Ken J. Chmiel, Reen Wu, Jonathan H. Widdicombe

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The goal of this study was to determine whether the extracellular regulated kinases (ERK1/2) are involved in leukocyte transmigration across airway epithelium and the associated changes in epithelial permeability. In vitro, we used formyl-methlonylleucyl-phenylalanine (fMLP) to induce migration of HL-60 cells (a human leukocyte cell line) across sheets of polarized Calu-3 airway epithelial cells and also to induce migration of human neutrophils across primary cultures of cow tracheal epithelial cells. In both systems, leukocyte migration decreased transepithelial electrical resistance (R te), increased epithelial permeability to albumin (Palb), and increased ERK1/2 phosphorylation in epithelial cells. Leukocyte migration and the associated changes in Rte, Palb, and ERK1/2 phosphorylation were inhibited by calphostin C, a blocker of protein kinase C (PKC), and by PD98059 (a blocker of ERK1/2). Leukocyte transmigration in rat tracheas in vivo was induced with fMLP, and was associated with increased P alb and phosphorylation of epithelial ERK1/2. Again, migration and the associated changes were inhibited by luminal PD98059 or calphostin C though neither agent affected rat leukocyte migration in Boyden chambers in vitro. We conclude that PKC and ERK1/2 pathways are activated in airway epithelial cells during migration of leukocytes and are important regulators of airway epithelial permeability.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number3
DOIs
StatePublished - Mar 2004

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ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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