Grant: Project Grant

The neutrophils are without doubt one of the key cells entering an injured heart. As such it is very important to understand how they live, how they die and whether there are good and bad neutrophils. Work from the 1960s and 1970s when techniques were very crude suggested that neutrophils only live 8 hrs in blood and then die mostly in places like liver, lung and spleen. However, this required that the neutrophils were taken out of the body, labeled and tracked after re-injection. The problem is that this activates the neutrophils and they start getting stuck in the capillaries of various organs. We have a way of tracking neutrophils without removing them from the body- mice that have a label just on neutrophils so that we can see in which organ they go to die. In addition, we have made mice that have neutrophils that become fluorescent when we shine ultraviolet light on them. Neither of these approaches activate the neutrophils and the results suggest that neutrophils do not die in places like lungs and liver but rather die in bone marrow. The neutrophils appear to live much longer (perhaps 72 hrs) and this is important because this means there are neutrophils that may either change their roles or have different functions. This challenges the dogma that the neutrophils were a single population that caused damage and we hypothesize that some neutrophils may have the job of repair. We will examine whether the neutrophils enter a heart injury and whether some are more or less inclined to repair an injury in the heart. We will examine whether neutrophils leave the injured heart and return to bone marrow and if they go back to the bone marrow whether they may cause the next generation of neutrophils to be educated to better repair the heart. This work will give us a better understanding of neutrophil biology and perhaps help us reprogram the neutrophils to better heal the heart.