Grant: CIHR New Investigator

When there is an infection or injury in the body, neutrophils, the most abundant white blood cells, will move from blood, across the blood vessel wall and toward the site of infection or injury. Normally, neutrophils kill bacteria. But in diseases such as sepsis, hemorrhage, myocardial infarction, or stroke, they damage or even kill our own cells. This harmful situation should be prevented. LSP1 (leukocyte-specific protein 1) is a protein inside white blood cells, including neutrophils. We recently found that LSP1 is also present in the blood vessel wall (endothelium) and that it controls neutrophil movement out of the blood vessel. We will use a sophisticated microscope to watch and measure this movement in mice. We will use mice bred specifically to lack LSP1, and compare them with normal mice with LSP1. We will use chemicals (called chemokines) to examine if the LSP1 in endothelium or in neutrophils is important in neutrophil movement within and across the vessel wall, and in the tissue. We will check how fast and how far the neutrophils move, how important the LSP1 in neutrophils and in endothelium is in the process, and if those chemokines use or bypass LSP1 in endothelium. We have the experience and skills of using the specialized microscope to watch directly the movement of neutrophils within the vessel wall and in the tissues. We are probably unique in Canada because we can use the microscope with special new techniques for doing the research and with the special mice having no LSP1 (which we can share with other scientists). Many inflammatory diseases are very difficult to treat. Migration out of the blood vessel is the most important step for neutrophils to move to the site of infection or injury. We focus on this step and will reveal the detailed mechanisms of how LSP1 works in endothelium and in neutrophils. Our research will provide clues to design and develop better drugs in the management of various vascular and inflammatory diseases.