HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/H1296    most recent 00687.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Waschke, J. Articles by Drenckhahn, D. Search for Related Content PubMed PubMed Citation Articles by Waschke, J. Articles by Drenckhahn, D.

Regulation of actin dynamics is critical for endothelial barrier functions

¹Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany; and ²Department of Human Physiology and Membrane Biology, School of Medicine, University of California, Davis, California

Submitted 12 July 2004 ; accepted in final form 27 October 2004

We tested the hypothesis that the equilibrium between F- and G-actin in endothelial cells modulates the integrity of the actin cytoskeleton and is important for the maintenance of endothelial barrier functions in vivo and in vitro. We used the actin-depolymerizing agent cytochalasin D and jasplakinolide, an actin filament (F-actin) stabilizing and promoting substance, to modulate the actin cytoskeleton. Low doses of jasplakinolide (0.1 µM), which we have previously shown to reduce the permeability-increasing effect of cytochalasin D, had no influence on resting permeability of single-perfused mesenteric microvessels in vivo as well as on monolayer integrity. The F-actin content of cultured endothelial cells remained unchanged. In contrast, higher doses (10 µM) of jasplakinolide increased permeability (hydraulic conductivity) to the same extent as cytochalasin D and induced formation of intercellular gaps in cultured myocardial endothelial (MyEnd) cell monolayers. This was accompanied by a 34% increase of F-actin and pronounced disorganization of the actin cytoskeleton in MyEnd cells. Furthermore, we tested whether an increase of cAMP by forskolin and rolipram would prevent the cytochalasin D-induced barrier breakdown. Conditions that increase intracellular cAMP failed to block the cytochalasin D-induced permeability increase in vivo and the reduction of vascular endothelial cadherin-mediated adhesion in vitro. Taken together, these data support the hypothesis that the state of polymerization of the actin cytoskeleton is critical for maintenance of endothelial barrier functions and that both depolymerization by cytochalasin D and hyperpolymerization of actin by jasplakinolide resulted in an increase of microvessel permeability in vivo. However, cAMP, which is known to support endothelial barrier functions, seems to work by mechanisms other than stabilizing F-actin.

permeability; actin; jasplakinolide; adenosine 3',5'-cylic monophosphate; vascular endothelia cadherin

This article has been cited by other articles:

				N. Schlegel and J. Waschke VASP is involved in cAMP-mediated Rac 1 activation in microvascular endothelial cells Am J Physiol Cell Physiol, March 1, 2009; 296(3): C453 - C462. [Abstract] [Full Text] [PDF]

				V. Solodushko, J. C. Parker, and B. Fouty Pulmonary Microvascular Endothelial Cells Form a Tighter Monolayer when Grown in Chronic Hypoxia Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 491 - 497. [Abstract] [Full Text] [PDF]

				S. Heyraud, M. Jaquinod, C. Durmort, E. Dambroise, E. Concord, J. P. Schaal, P. Huber, and D. Gulino-Debrac Contribution of Annexin 2 to the Architecture of Mature Endothelial Adherens Junctions Mol. Cell. Biol., March 1, 2008; 28(5): 1657 - 1668. [Abstract] [Full Text] [PDF]

				K. Muller-Marschhausen, J. Waschke, and D. Drenckhahn Physiological hydrostatic pressure protects endothelial monolayer integrity Am J Physiol Cell Physiol, January 1, 2008; 294(1): C324 - C332. [Abstract] [Full Text] [PDF]

				N. Schlegel, S. Burger, N. Golenhofen, U. Walter, D. Drenckhahn, and J. Waschke The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier stabilization Am J Physiol Cell Physiol, January 1, 2008; 294(1): C178 - C188. [Abstract] [Full Text] [PDF]

				J. Waschke, V. Spindler, P. Bruggeman, D. Zillikens, G. Schmidt, and D. Drenckhahn Inhibition of Rho A activity causes pemphigus skin blistering J. Cell Biol., December 4, 2006; 175(5): 721 - 727. [Abstract] [Full Text] [PDF]

				G. L. Bentz, M. Jarquin-Pardo, G. Chan, M. S. Smith, C. Sinzger, and A. D. Yurochko Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naive Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV J. Virol., December 1, 2006; 80(23): 11539 - 11555. [Abstract] [Full Text] [PDF]

				M. Condrescu and J. P. Reeves Actin-dependent regulation of the cardiac Na+/Ca2+ exchanger Am J Physiol Cell Physiol, March 1, 2006; 290(3): C691 - C701. [Abstract] [Full Text] [PDF]

				J. W. Breslin, H. Sun, W. Xu, C. Rodarte, A. B. Moy, M. H. Wu, and S. Y. Yuan Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H741 - H750. [Abstract] [Full Text] [PDF]

				F. Baffert, T. Le, G. Thurston, and D. M. McDonald Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H107 - H118. [Abstract] [Full Text] [PDF]