Neutrophils re-entering the circulation from a primary site of inflammation: Physiological or pathological?

Neutrophils are the most abundant type of white cells in human blood, and form a critical component of the host's defense mechanism against infections and injury. To achieve this critical role, neutrophils move rapidly from blood vessels into damaged tissues as guided by locally generated danger signals. Although considered a one-way trafficking process, we have found that in some cases neutrophils entering tissues can move in a reverse manner, and re-enter the blood stream in an activated state. These "rogue" white cells can then move to other parts of the body (e.g. lungs) and cause damage. Here, we plan to use imaging techniques that enable us to observe the movement of neutrophils in different experimental models of inflammation, to gain an in-depth understanding of the properties of this cell population. The findings could lead to the development of drugs aimed at reducing life-threatening complications of diseases, most notably in ageing.