Rogue Blood Cells Contribute to Postsurgery Organ Damage

A new study sheds light on how rogue super-activated neutrophils reenter the blood stream, causing damage to organs seemingly unconnected to the surgical injury.

Researchers at Queen Mary University of London (United Kingdom) used real-time three-dimensional (3D) confocal imaging to examine the polarized transendothelial migration (TEM) of blood neutrophils through endothelial cells (ECs) lining the venular lumen. While TEM is usually in a luminal-to-abluminal direction, the researchers found that neutrophils also had disrupted polarized TEM--either hesitant or even reversed--in inflammation after ischemia-reperfusion injury.

These reverse direction migrations were characterized by lower expression of junctional adhesion molecule C (JAM-C) at EC junctions. When the researchers temporarily blocked the blood vessels, mimicking the trauma experienced by patients undergoing major surgery, JAM-C was lost from the blood vessels. When this happened, the neutrophils seemed to lose their way. Cells that had already exited blood vessels returned to the blood stream and damaged other parts of the body. In particular, the researchers found that these confused but highly activated neutrophils lodged into blood vessels in the lungs, causing damage.

According to the researchers, the JAM-C molecule and the properties of these rogue neutrophils could lead to the development of drugs aimed at reducing life-threatening complications following major surgeries such as inflammation of the lungs. The study was published early online on June 26, 2011, in Nature Immunology.

“Neutrophils are usually our first line of defense against infection but they have the ability to cause many diseases. As we learn more about the complex processes that protect us against infections we also find ways of tackling inflammatory diseases where white blood cells are inappropriately switched on,” said lead author Prof. Sussan Nourshargh, PhD. “The neutrophils that behave this way are very different from normal blood neutrophils in that they are highly activated and fully capable of causing damage to other organs.”

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Queen Mary University of London