A new study has shed light on a little-known weapon in the body’s defensive arsenal, one that plays a vital role in healing when the skin is breached by a cut or bite.
Neutrophil extracellular traps, or NETs, form when white blood cells called neutrophils self-destruct and form a sticky web to catch invading germs. According to a paper published in the Sept. 7 Proceedings of the National Academy of Sciences, these NETs also carry out another important function: providing a structure to support the formation of blood clots. In this previously unknown role, NETs aid in closing the wound at the same time they capture pathogens that have entered the body.
The research team from the Immune Disease Institute (the Program in Cellular and Molecular Medicine at Children’s Hospital Boston) flooded NETs with blood and recorded the response. The defensive webs began recruiting red blood cells and collecting platelets to form a clot while also binding plasma proteins to keep the clot stable.
Denisa Wagner, HMS professor of pathology at IDI, who worked on the study explained: “If a tiger bites you with dirty teeth, not only does the infection cause an inflammatory response, but you also need to close and repair the wound. NETs both contain infection and provide a matrix with which to close the wound and promote healing.”
Still, Wagner said, little is known about these mysterious but important foot soldiers of the immune system. It is not yet clear when NETs form or how the process that causes neutrophils to shut down and turn into NETs operates. Further study is also needed to understand how NETs fit into the broader function of initiating, maintaining, then breaking down blood clots.
Wagner believes the group’s work could have implications for treating conditions ranging from deep vein thrombosis to lupus, sickle cell disease and wound infection.
“The red flag common to all these conditions is excessive cellular adhesion in blood vessels, which could be promoted by neutrophils going into the NET suicide cycle.”
While more research is needed to determine whether NETs might serve as the basis of new therapies, the study’s lead author Tobias Fuchs, research fellow in pathology at IDI, hopes this work will highlight new directions for research on a range of disorders.
“Clot formation is helpful in order to prevent blood loss after wounding,” he said. On the other hand, there are circumstances when the process poses risks. “In cardiovascular diseases, blood clots may form within arteries or veins.”
For more information, students may contact Denisa Wagner at wagner@idi.harvard.edu.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: National Heart, Lung, and Blood Institute of the National Institutes of Health and Deutsche Forschungsgemeinschaft, Germany; the authors are solely responsible for the content of this work.
Disclaimer: The researchers are unable to provide treatment recommendations for individual cases.
