Grant: Operating Grant

White cells get into different tissues to either kill bacteria or, when inappropriately activated, to cause damage as occurs in hepatitis and inflammatory bowel disease. If we could block their recruitment into tissues we might be able to prevent some of the diseases. Our understanding of how white cells are recruited is incomplete, but we now have a brand new imaging system that lets us look in blood vessels of living mice at all the different white cells. We will look at how different white cells enter the liver vasculature during various inflammatory and infectious conditions. There are at least 2 types of white cells that live in the blood vessels of the liver that can help to detect infections and injuries and release factors that initiate inflammation. We can watch the behavior of these cells. Using microscopy approaches that allow us to watch white cells in blood vessels we will assess how important different molecules are for white cells to stop in the liver blood vessels despite lots of flow pushing them out of the liver. In addition, most investigators have examined the role of recruitment pathways in simple systems but not in complex conditions like liver disease. We will investigate how white cells move into this tissue and whether any of the recruitment pathways are important in inflammation. Finally, white cells include neutrophils, monocytes, Kupffer cells as well as iNKT cells which are a subset of lymphocytes. We now have different strains of mice in which each of the cell types glow. This will help tell us which white cells are adhering via which recruitment pathways in which inflammatory conditions and may reveal strategies to reduce the over-exuberant inflammatory response.