| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224
The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.
cytoskeleton; endothelium; actomyosin contraction; actin-binding proteins; acute lung injury
This article has been cited by other articles:
|
|
 |
|
  Y.-C. Chang, P. Nalbant, J. Birkenfeld, Z.-F. Chang, and G. M. Bokoch GEF-H1 Couples Nocodazole-induced Microtubule Disassembly to Cell Contractility via RhoA Mol. Biol. Cell, May 1, 2008; 19(5): 2147 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kamp, X. Sun, and J. G. N. Garcia Making Genomics Functional: Deciphering the Genetics of Acute Lung Injury Proceedings of the ATS, April 15, 2008; 5(3): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. VANDENBROUCKE, D. MEHTA, R. MINSHALL, and A. B. MALIK Regulation of Endothelial Junctional Permeability Ann. N.Y. Acad. Sci., March 1, 2008; 1123(1): 134 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Troyanovsky, D. F. Alvarez, J. A. King, and K. L. Schaphorst Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L266 - L275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wu, H. Chen, M. F. Alexeyev, J. A. C. King, T. M. Moore, T. Stevens, and R. D. Balczon Microtubule Motors Regulate ISOC Activation Necessary to Increase Endothelial Cell Permeability J. Biol. Chem., November 30, 2007; 282(48): 34801 - 34808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Omori, Y. Shikata, K. Sarai, N. Watanabe, J. Wada, N. Goda, N. Kataoka, K. Shikata, and H. Makino Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1523 - C1531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Singleton, R. Salgia, L. Moreno-Vinasco, J. Moitra, S. Sammani, T. Mirzapoiazova, and J. G. N. Garcia CD44 Regulates Hepatocyte Growth Factor-mediated Vascular Integrity: ROLE OF c-Met, Tiam1/Rac1, DYNAMIN 2, AND CORTACTIN J. Biol. Chem., October 19, 2007; 282(42): 30643 - 30657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Csortos, I. Kolosova, and A. D. Verin Regulation of vascular endothelial cell barrier function and cytoskeleton structure by protein phosphatases of the PPP family Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L843 - L854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su, D. Kondrikov, and E. R. Block beta-Actin: A Regulator of NOS-3 Sci. Signal., September 18, 2007; 2007(404): pe52 - pe52. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Behling-Kelly, D. McClenahan, K. S. Kim, and C. J. Czuprynski Viable "Haemophilus somnus" Induces Myosin Light-Chain Kinase-Dependent Decrease in Brain Endothelial Cell Monolayer Resistance Infect. Immun., September 1, 2007; 75(9): 4572 - 4581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Birukova, E. Alekseeva, A. Mikaelyan, and K. G. Birukov HGF attenuates thrombin-induced endothelial permeability by Tiam1-mediated activation of the Rac pathway and by Tiam1/Rac-dependent inhibition of the Rho pathway FASEB J, September 1, 2007; 21(11): 2776 - 2786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mammoto, S. M. Parikh, A. Mammoto, D. Gallagher, B. Chan, G. Mostoslavsky, D. E. Ingber, and V. P. Sukhatme Angiopoietin-1 Requires p190 RhoGAP to Protect against Vascular Leakage in Vivo J. Biol. Chem., August 17, 2007; 282(33): 23910 - 23918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Singleton, L. Moreno-Vinasco, S. Sammani, S. L. Wanderling, J. Moss, and J. G. N. Garcia Attenuation of Vascular Permeability by Methylnaltrexone: Role of mOP-R and S1P3 Transactivation Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 222 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, I. Malyukova, V. Poroyko, and K. G. Birukov Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L199 - L211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nguyen, A. J. Pace, and B. H. Koller Mice lacking NKCC1 are protected from development of bacteremia and hypothermic sepsis secondary to bacterial pneumonia J. Exp. Med., June 11, 2007; 204(6): 1383 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Rossi, A. V. Velentza, D. M. Steinhorn, D. M. Watterson, and M. S. Wainwright MLCK210 gene knockout or kinase inhibition preserves lung function following endotoxin-induced lung injury in mice Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1327 - L1334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D'hondt, S. P. Srinivas, J. Vereecke, and B. Himpens Adenosine Opposes Thrombin-Induced Inhibition of Intercellular Calcium Wave in Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1518 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guo, P. A. Singleton, A. Rowshan, M. Gucek, R. N. Cole, D. R. M. Graham, J. E. Van Eyk, and J. G. N. Garcia Quantitative Proteomics Analysis of Human Endothelial Cell Membrane Rafts: Evidence of MARCKS and MRP Regulation in the Sphingosine 1-Phosphate-induced Barrier Enhancement Mol. Cell. Proteomics, April 1, 2007; 6(4): 689 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. McLaughlin, M. M. Patterson, and A. B. Malik Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization PNAS, March 27, 2007; 104(13): 5662 - 5667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Singh, N. Knezevic, G. U. Ahmmed, V. Kini, A. B. Malik, and D. Mehta G{alpha}q-TRPC6-mediated Ca2+ Entry Induces RhoA Activation and Resultant Endothelial Cell Shape Change in Response to Thrombin J. Biol. Chem., March 16, 2007; 282(11): 7833 - 7843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Su, M. Hodnett, N. Wu, A. Atakilit, C. Kosinski, M. Godzich, X. Z. Huang, J. K. Kim, J. A. Frank, M. A. Matthay, et al. Integrin {alpha}vbeta5 Regulates Lung Vascular Permeability and Pulmonary Endothelial Barrier Function Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 377 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Ranaivo, N. Carusio, R. Wangensteen, P. Ohlmann, C. Loichot, A. Tesse, K. Chalupsky, I. Lobysheva, J. Haiech, D. M. Watterson, et al. Protection Against Endotoxic Shock as a Consequence of Reduced Nitrosative Stress in MLCK210-Null Mice Am. J. Pathol., February 1, 2007; 170(2): 439 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D'hondt, R. Ponsaerts, S. P. Srinivas, J. Vereecke, and B. Himpens Thrombin Inhibits Intercellular Calcium Wave Propagation in Corneal Endothelial Cells by Modulation of Hemichannels and Gap Junctions Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 120 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Meyer and J. G. N. Garcia Wading into the Genomic Pool to Unravel Acute Lung Injury Genetics Proceedings of the ATS, January 1, 2007; 4(1): 69 - 76. [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]
|
|
|
|
|
|
D. J. Angelini, S.-W. Hyun, D. N. Grigoryev, P. Garg, P. Gong, I. S. Singh, A. Passaniti, J. D. Hasday, and S. E. Goldblum TNF-{alpha} increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1232 - L1245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Usatyuk, N. L. Parinandi, and V. Natarajan Redox Regulation of 4-Hydroxy-2-nonenal-mediated Endothelial Barrier Dysfunction by Focal Adhesion, Adherens, and Tight Junction Proteins J. Biol. Chem., November 17, 2006; 281(46): 35554 - 35566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Singleton, S. M. Dudek, S.-F. Ma, and J. G. N. Garcia Transactivation of Sphingosine 1-Phosphate Receptors Is Essential for Vascular Barrier Regulation: NOVEL ROLE FOR HYALURONAN AND CD44 RECEPTOR FAMILY J. Biol. Chem., November 10, 2006; 281(45): 34381 - 34393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Mirzapoiazova, I. Kolosova, P. V. Usatyuk, V. Natarajan, and A. D. Verin Diverse effects of vascular endothelial growth factor on human pulmonary endothelial barrier and migration Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L718 - L724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Maeda, Y.-i. Ozaki, S. Sivakumaran, T. Akiyama, H. Urakubo, A. Usami, M. Sato, K. Kaibuchi, and S. Kuroda Ca-independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response. Genes Cells, September 1, 2006; 11(9): 1071 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Lu, E. O. Harrington, H. Jackson, N. Morin, C. Shannon, and S. Rounds Transforming growth factor-beta1-induced endothelial barrier dysfunction involves Smad2-dependent p38 activation and subsequent RhoA activation J Appl Physiol, August 1, 2006; 101(2): 375 - 384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Gavara, R. Sunyer, P. Roca-Cusachs, R. Farre, M. Rotger, and D. Navajas Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy J Appl Physiol, August 1, 2006; 101(2): 512 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Paria, A. M. Bair, J. Xue, Y. Yu, A. B. Malik, and C. Tiruppathi Ca2+ Influx Induced by Protease-activated Receptor-1 Activates a Feed-forward Mechanism of TRPC1 Expression via Nuclear Factor-{kappa}B Activation in Endothelial Cells J. Biol. Chem., July 28, 2006; 281(30): 20715 - 20727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Su, Z. Cui, Z. Li, and E. R. Block Calpain-2 regulation of VEGF-mediated angiogenesis FASEB J, July 1, 2006; 20(9): 1443 - 1451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Trepat, F. Puig, N. Gavara, J. J. Fredberg, R. Farre, and D. Navajas Effect of stretch on structural integrity and micromechanics of human alveolar epithelial cell monolayers exposed to thrombin Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1104 - L1110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kumar, I. Z. Maxwell, A. Heisterkamp, T. R. Polte, T. P. Lele, M. Salanga, E. Mazur, and D. E. Ingber Viscoelastic Retraction of Single Living Stress Fibers and Its Impact on Cell Shape, Cytoskeletal Organization, and Extracellular Matrix Mechanics Biophys. J., May 15, 2006; 90(10): 3762 - 3773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. van de Visse, M. van der Heijden, J. Verheij, G. P. van Nieuw Amerongen, V. W. M. van Hinsbergh, A. R. J. Girbes, and A. B. J. Groeneveld Effect of prior statin therapy on capillary permeability in the lungs after cardiac or vascular surgery. Eur. Respir. J., May 1, 2006; 27(5): 1026 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, S. Chatchavalvanich, A. Rios, K. Kawkitinarong, J. G.N. Garcia, and K. G. Birukov Differential Regulation of Pulmonary Endothelial Monolayer Integrity by Varying Degrees of Cyclic Stretch Am. J. Pathol., May 1, 2006; 168(5): 1749 - 1761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gao, A. Grant, I. Halder, R. Brower, J. Sevransky, J. P. Maloney, M. Moss, C. Shanholtz, C. R. Yates, G. U. Meduri, et al. Novel Polymorphisms in the Myosin Light Chain Kinase Gene Confer Risk for Acute Lung Injury Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 487 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Romer, K. G. Birukov, and J. G.N. Garcia Focal adhesions: paradigm for a signaling nexus. Circ. Res., March 17, 2006; 98(5): 606 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, D. Adyshev, B. Gorshkov, G. M. Bokoch, K. G. Birukov, and A. D. Verin GEF-H1 is involved in agonist-induced human pulmonary endothelial barrier dysfunction Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L540 - L548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tzima Role of Small GTPases in Endothelial Cytoskeletal Dynamics and the Shear Stress Response Circ. Res., February 3, 2006; 98(2): 176 - 185. [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]
|
|
|
|
|
|
M. Holinstat, N. Knezevic, M. Broman, A. M. Samarel, A. B. Malik, and D. Mehta Suppression of RhoA Activity by Focal Adhesion Kinase-induced Activation of p190RhoGAP: ROLE IN REGULATION OF ENDOTHELIAL PERMEABILITY J. Biol. Chem., January 27, 2006; 281(4): 2296 - 2305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kondrikov, H.-R. Han, E. R. Block, and Y. Su Growth and density-dependent regulation of NO synthase by the actin cytoskeleton in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L41 - L50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Usatyuk and V. Natarajan Regulation of reactive oxygen species-induced endothelial cell-cell and cell-matrix contacts by focal adhesion kinase and adherens junction proteins Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L999 - L1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Han, M. Lodyga, and M. Liu Ventilator-induced Lung Injury: Role of Protein-Protein Interaction in Mechanosensation Proceedings of the ATS, October 1, 2005; 2(3): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Singleton, S. M. Dudek, E. T. Chiang, and J. G. N. Garcia Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and {alpha}-actinin FASEB J, October 1, 2005; 19(12): 1646 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cai Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences Cardiovasc Res, October 1, 2005; 68(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. An, C. M. Pennella, A. Gonnabathula, J. Chen, N. Wang, M. Gaestel, P. M. Hassoun, J. J. Fredberg, and U. S. Kayyali Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho kinase-dependent pathways Am J Physiol Cell Physiol, September 1, 2005; 289(3): C521 - C530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Nelson, R. P. Jean, J. L. Tan, W. F. Liu, N. J. Sniadecki, A. A. Spector, and C. S. Chen From the Cover: Emergent patterns of growth controlled by multicellular form and mechanics PNAS, August 16, 2005; 102(33): 11594 - 11599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mehta Lysophosphatidylcholine: an enigmatic lysolipid Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L174 - L175. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Caironi, F. Ichinose, R. Liu, R. C. Jones, K. D. Bloch, and W. M. Zapol 5-Lipoxygenase Deficiency Prevents Respiratory Failure during Ventilator-induced Lung Injury Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 334 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. A. Kolosova, T. Mirzapoiazova, D. Adyshev, P. Usatyuk, L. H. Romer, J. R. Jacobson, V. Natarajan, D. B. Pearse, J. G.N. Garcia, and A. D. Verin Signaling Pathways Involved in Adenosine Triphosphate-Induced Endothelial Cell Barrier Enhancement Circ. Res., July 22, 2005; 97(2): 115 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gorovoy, J. Niu, O. Bernard, J. Profirovic, R. Minshall, R. Neamu, and T. Voyno-Yasenetskaya LIM Kinase 1 Coordinates Microtubule Stability and Actin Polymerization in Human Endothelial Cells J. Biol. Chem., July 15, 2005; 280(28): 26533 - 26542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Birukova, K. G. Birukov, B. Gorshkov, F. Liu, J. G. N. Garcia, and A. D. Verin MAP kinases in lung endothelial permeability induced by microtubule disassembly Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L75 - L84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Vlahakis and R. D. Hubmayr Cellular Stress Failure in Ventilator-injured Lungs Am. J. Respir. Crit. Care Med., June 15, 2005; 171(12): 1328 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Warfel, A. D. Steele, and F. D'Agnillo Anthrax Lethal Toxin Induces Endothelial Barrier Dysfunction Am. J. Pathol., June 1, 2005; 166(6): 1871 - 1881. |
