THE MICROTUBULE SYSTEM IN ENDOTHELIAL BARRIER DYSFUNCTION: DISASSEMBLY OF PERIPHERAL MICROTUBULES AND
MICROTUBULES REORGANIZATION IN INTERNAL CYTOPLASM
K. M. Smurova,1 A. A. Birukova,2 A. D. Verin,3
I. B. Alieva 1, *
1 A. N. Belozersky Institute, Moscow State University, 2 Department of Medicine,
Section of Pulmonary and Critical Care Medicine, University of Chicago, USA, and 3 Vascular Biology
Center, Medical College of Georgia, Augusta, USA;
* e-mail: irina_alieva@belozersky.msu.ru
Endothelial cell barrier dysfunction is often associated with dramatic cytoskeletal reorganization, activation
of actomyosin contraction and finally gap formation. At present time the role of microtubules in endothelial cell
barrier regulation is not fully understood, however a number of observations allow to assume that microtubules
reaction is the extremely important part in development of endothelial dysfunction. These observations have
been forced us to examine the role of microtubule system reorganization in endothelial cell barrier regulation.
In quiescent endothelial cells microtubule density is the highest in the centrosome region and insignificant near
the cell margin. The analysis of microtubules distribution after specific antibodies staining using the method of
measurement of their fluorescence intensity has shown that in control endothelial cells the reduction of fluorescence
intensity from the cell center to its periphery is described by the equation of an exponential regression.
The hormone agent, thrombin (25 nM), causes rapid increase of endothelial cell barrier permeability accompanied
by fast decrease in quantity of peripheral microtubules and reorganization of microtubule system in internal
cytoplasm of endothelial cells (the decrease of fluorescence intensity is described by the equation of linear regress
already through 10 min after the beginning of the treatment). Both effects are reversible-through 60 min
after the beginning of the treatment the microtubule network does not differ from normal one, so the microtubule
system is capable to adapt for influence of a natural regulator thrombin. The microtubules reaction develops
more quickly, than reorganization of the actin filaments system, which responsible for the subsequent changes
in the cell shape during barrier dysfunction. Apparently, the microtubules are the first part in a circuit of the
reactions leading to the pulmonary endothelial cell barrier compromise.
Key words: pulmonary endothelium, endothelial barrier function, endothelial barrier
dysfunction, thrombin, actin filaments, microtubules
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