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Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin.
- Source :
-
Biophysical journal [Biophys J] 2008 Jul; Vol. 95 (2), pp. 886-94. Date of Electronic Publication: 2008 Apr 11. - Publication Year :
- 2008
-
Abstract
- Disruption of pulmonary endothelial cell (EC) barrier function is a critical pathophysiologic event in highly morbid inflammatory conditions such as sepsis and acute respiratory disease stress syndrome. Actin cytoskeleton, an essential regulator of endothelial permeability, is a dynamic structure whose stimuli-induced rearrangement is linked to barrier modulation. Here, we used atomic force microscopy to characterize structural and mechanical changes in the F-actin cytoskeleton of cultured human pulmonary artery EC in response to both barrier-enhancing (induced by sphingosine 1-phosphate (S1P)) and barrier-disrupting (induced by thrombin) conditions. Atomic force microscopy elasticity measurements show differential effects: for the barrier protecting molecule S1P, the elastic modulus was elevated significantly on the periphery; for the barrier-disrupting molecule thrombin, on the other hand, it was elevated significantly in the central region of the cell. The force and elasticity maps correlate with F-actin rearrangements as identified by immunofluorescence analysis. Significantly, reduced expression (via siRNA) of cortactin, an actin-binding protein essential to EC barrier regulation, resulted in a shift in the S1P-mediated elasticity pattern to more closely resemble control, unstimulated endothelium.
- Subjects :
- Actins chemistry
Cortactin chemistry
Elasticity
Endothelium, Vascular chemistry
Humans
Lysophospholipids chemistry
Microscopy, Atomic Force methods
Pulmonary Artery chemistry
Sphingosine chemistry
Sphingosine physiology
Stress, Mechanical
Thrombin chemistry
Actins physiology
Cortactin physiology
Endothelium, Vascular physiology
Lysophospholipids physiology
Pulmonary Artery physiology
Sphingosine analogs & derivatives
Thrombin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1542-0086
- Volume :
- 95
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biophysical journal
- Publication Type :
- Academic Journal
- Accession number :
- 18408039
- Full Text :
- https://doi.org/10.1529/biophysj.107.127167