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Published ahead of print on July 3, 2003, doi:10.1165/rcmb.2003-0053OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 261-270

A more recent version of this article appeared on March 1, 2004
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Submitted on February 19, 2003
Revised on June 30, 2003

Role of ERK in the increase in airway epithelial permeability during leukocyte transmigration

Vladimir B Serikov1, Hyon Choi1, Kenneth J Chmiel2, Reen Wu2, and Jonathan H Widdicombe3*

1 Pulmonary Lab, Children's Hospital Oakland Research Institute, Oakland, CA, USA, 2 Department of Medicine, University of California, Davis, CA, USA, 3 Department of Human Physiology, University of California, Davis, CA, USA

* To whom correspondence should be addressed. E-mail: jwiddicombe{at}ucdavis.edu.

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-methionyl-leucyl-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 (Rte), 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 Palb 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.






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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society.