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White Blood Cells Move Like Millipedes in Blood Vessels

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[Apparently 'shear force' is necessary for the WBC to function properly.]

Weizmann Institute Scientists Show White Blood Cells Move like Millipedes

04.05.2009

How do white blood cells †" immune system ‘soldiers’ †" get to the site of

infection or injury? To do so, they must crawl swiftly along the lining of the

blood vessel †" gripping it tightly to avoid being swept away in the blood flow

†" all the while searching for temporary ‘road signs’ made of special

adhesion molecules that let them know where to cross the blood vessel barrier so

they can get to the damaged tissue.

In research recently published in the journal Immunity, Prof. Ronen Alon and his

research student Ziv Shulman of the Weizmann Institute’s Immunology Department

show how white blood cells advance along the length of the endothelial cells

lining the blood vessels. Current opinion maintains that immune cells advance

like inchworms, but Alon’s new findings show that the rapid movement of the

white blood cells is more like that of millipedes. Rather than sticking front

and back, folding and extending to push itself forward, the cell creates

numerous tiny ‘legs’ no more than a micron in length †" adhesion points,

rich in adhesion molecules (named LFA-1) that bind to partner adhesion molecules

present on the surface of the blood vessels. Tens of these legs attach and

detach in sequence within seconds †" allowing them to move rapidly while

keeping a good grip on the vessels’ sides.

Next, the scientists turned to the Institute’s Electron Microscopy Unit.

Images produced by scanning and transmission electron microscopes, taken by Drs.

Eugenia Klein and Vera Shinder, showed that upon attaching to the blood vessel

wall, the white blood cell legs ‘dig’ themselves into the endothelium,

pressing down on its surface. The fact that these legs †" which had been

thought to appear only when the cells leave the blood vessels †" are used in

crawling the vessel lining suggests that they may serve as probes to sense exit

signals. The researchers found that the shear force created by the blood flow

was necessary for the legs to embed themselves. Without the thrust of the

rushing blood, the white blood cells couldn’t sense the exit signals or get to

the site of the injury. These results explain Alon’s previous findings that

the blood’s shear force is essential for the white blood cells to exit the

blood vessel wall. The present study suggests that shear forces cause their

adhesion molecules to enter highly active states. The scientists believe that

the tiny legs are trifunctional: Used for gripping, moving and sensing distress

signals from the damaged tissue.

In future studies, the scientists plan to check whether it is possible to

regulate aggressive immune reactions (such as in autoimmune diseases) by

interrupting the ‘digging’ of immune cell legs into the endothelium. They

also plan to investigate whether cancerous blood cells metastasize through the

blood stream using similar mechanisms in order to exit the blood vessels and

enter different tissues.

Weizmann Institute news releases are posted on the World Wide Web at

http://wis-wander.weizmann.ac.il/, and are also available at

http://www.eurekalert.org/.

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