Abstract
Recently we discovered an association between local lamellipodia formation/turnover and endothelial barrier function. To determine cause‐effect, we tested the hypothesis that selective blockade of lamellipodia formation with the myosin II inhibitor (−)blebbistatin would disrupt endothelial barrier integrity. We also investigated whether myosin II inhibition affects sphingosine‐1‐phosphate (S1P)‐induced endothelial barrier enhancement. Transendothelial electrical resistance (TER) of confluent cultured human umbilical vein endothelial cells (HUVEC) served as an index of barrier function. HUVEC expressing GFP‐actin were used to study local lamellipodia dynamics. The results show that 100 μM (−)blebbistatin caused a significant decrease in TER, while (+)blebbistatin caused no change from baseline. In addition, (−)blebbistatin, caused local lamellipodia protrusion frequency to drop nearly 90%, while (+)blebbistatin caused no change. S1P (2 μM) increased TER and caused a brief, coordinated protrusion of the edges of individual endothelial cells. Pretreatment with (−)blebbistatin did not inhibit the S1P‐induced increase in TER. Our data indicate that MLC‐2‐driven local lamellipodia contribute to endothelial barrier function. However, an myosin II‐independent mechanism drives S1P‐induced edge protrusions and endothelial barrier enhancement. Supported by NIH R01HL098215.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
