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Endothelium, heal thyself
Date:5/16/2013

lli, PhD, revealed that in response to micrometer-scale disruptions caused by the transmigrating leukocytes, the endothelial cells were generating unique ventral lamellipodia structures, which were then migrating to the sites of the micro-wounds to close them up. "The ventral lamellipodia were responding to the sensation of an acute loss of preexisting isometric tension," explains Martinelli, a senior scientist in the Carman laboratory, who compares the cell to a circus tent tethered in place by strategically placed ropes and stakes.

"If you cut one of the ropes holding up the tent, two things will happen," she adds. "First the part of the tent that was under tension will undergo a recoil which will lead to a relaxation, leaving one part of the tent untethered and flapping in the breeze. At the same time, the remaining sets of ropes and stakes will have to bear the extra load. In the case of the endothelial cells, this translates to a force loading event."

Existing studies have focused almost exclusively on force loading (physical pulling or tugging on cells) as response triggers. But by using new devices, the team was able to push, prod, stretch and unstretch cells in very specific ways. "Our experiments told us that endothelial micro-wounding is actually a tension-loss signal [i.e. force unloading] and that this signal cued the recovery response," adds Carman. This response, he adds, is fundamentally dependent on proteins (i.e. NADPH oxidases) that can generate reactive oxygen species (ROS), specifically hydrogen peroxide.

ROS are widely implicated in causing cellular, tissue and organ damage when present at excessive levels in the body. But, these findings show that low levels of these molecules when produced in discrete locations within the cell are highly protective. "It's tempting to speculate that excess ROS causes vascular breakdown by short-circuiting the recuperative response process and creating 'white noise' that dis-coord
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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