Immune-cell Membrane Trafficking

Organ failure following trauma is a leading cause of morbidity and mortality. It appears
that the development of organ failure is a direct result of an altered immune response.
This altered response results in the production of circulating factors in the blood that
causes direct injury to the injured patients' organs. The mechanism in which this altered
immune response occurs is unknown. Based on work we have performed in our laboratory, we
believe that this response is initiated on the cell membrane of particular immune cells
known as macrophages. Although the cell membrane may appear uniform, it is not. The
membrane is composed of specific segments that allow proteins to associate with each other
forming receptors that are required for immune cell activation. These specific membrane
components are composed of various lipids and cholesterol, and have been termed lipid rafts.
Based on our laboratory work it appears that these lipid rafts can be altered following
injury. In particular both the lipid and protein content within these raft segments may be
altered allowing immune cells to become active leading to the production of factors that
directly injure normal cells and organs. Thus, we plan to examine if these laboratory
findings can be seen in patients suffering from trauma who develop clinical organ failure at
Harborview Medical Center. If this is accomplished, this data will lead to the development
of both prognostic and therapeutic interventions for the optimal care of injured patient