Characterization of Down-Regulated Adhesion Systems

Jutila, Mark

Abstract

Leukocyte migration into tissues occurs during all types of inflammatory events and is a critical component of host responses to infectious agents and some tumors. In some instances, the inflammatory response becomes uncontrolled which leads to chronic inflammatory diseases, such as arthritis. The process of leukocyte migration into tissues (extravasation) involves 3 distinct phases: 1) an initial interaction between the cell in the blood and the vascular endothelium, represented by rolling; 2) subsequent tight adhesion; and 3) eventual transendothelial migration. Each of these phases are controlled by highly-specific receptor-ligand interactions. The long range goal of our research is to characterize the regulation of the leukocyte adhesion molecules that control the first interaction with the vascular endothelium. Our earlier studies showed that receptors regulating this event, such as homing receptor (now called L-selectin), are rapidly down- regulated from the cell surface during subsequent phases of the extravasation process. The characterize the molecular mechanism that controls the expression of these molecules, and define any potential physical association of down-regulated adhesion receptors with other surface proteins, such as the leukocyte integrins. MBRS students will participate in each phase of these studies and will be trained in modern techniques of molecular immunology. They eventually will develop the ability to analyze data and design their own experiments. By their second year in the laboratory, it is expected that they present their research findings at scientific meetings, and, in most situations, their data will be included in or form the basis of a research manuscript.