ABSTRACT

The endothelial cells (EC) lining the vessels are in close contact with each other, rendering the vascular wall into a tight barrier, which control such diverse processes as vascular tone, homeostasis, adhesion of platelets and leukocytes to the vascular wall and permeability of vascular wall for cells and fl uids (Bazzoni and Dejana 2004, Dudek and Garcia 2001, Komarova

1A.N. Belozersky Institute of Physical and Chemical Biology, Moscow State University, Moscow, Russia. 2Department of Histology, Cytology and Embryology, Medical Faculty People’s Friendship University of Russia, Moscow, Russia. 3Vascular Biology Center, Georgia Health Science University, Augusta, GA 30912, USA. 4Pulmonary and Critical Care Medicine, Georgia Health Science University, Augusta, GA 30912, USA. aEmail: AVERIN@georgiahealth.edu *Corresponding author

and Malik 2010, Ware and Matthay 2000). Lung endothelium regulates movement of fl uid, macromolecules, and leukocytes into the interstitium and subsequently into the alveolar air spaces. The integrity of the pulmonary EC monolayer, therefore, is a critical requirement for preservation of pulmonary function. This barrier is dynamic and highly susceptible to the regulation, by various stimuli, of physiological and pathological origin. Any breach in the EC barrier results in leakage of fl uid from the lumen of the vessels into the interstitial tissue and/or alveolar lumen, severely impairing gas exchange. Disruption of endothelial barrier occurs during infl ammatory disease states such as acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), which remains a major cause of morbidity and mortality with an overall mortality rate of 30-40% (Ware and Matthay 2000), results in the uncontrolled movement of fl uid and macromolecules into the interstitium and pulmonary air spaces causing pulmonary edema (Ermert et al. 1995). Data of literature have proved that normal functioning of the endothelial barrier is provided by the balance between contracting and stretching forces generated by EC cytoskeleton (Bogatcheva and Verin 2008, Dudek and Garcia 2001, Komarova et al. 2007). In this review, we will analyze the cytoskeletal elements whose reorganization affects endothelial permeability, and emphasize the role of microtubules/microfi lament crosstalk in lung EC barrier regulation.