Research progress on this Physician Scientist Award for Dentists has included the continuation of our initial studies on the role of vascular endothelium in immune and inflammatory reactions, as originally proposed. The guinea pig has served as an ideal experimental animal model for our studies to date, particularly the use of inbred strains 2 and 13 animals as sources of various leukocyte populations as well as of vascular endothelial cells, permitting the use of a completely syngeneic system. We have established in vitro cloned populations of vascular endothelial cells from both large vessels and the microvasculature. The use of such cloned populations (derived from a single precursor cell and maintained under strictly isologous conditions in vitro), devoid of any contaminating cell types whatsoever, has provided a unique opportunity to examine the immune function of endothelial cells. We have characterized functionally and ultrastructurally various endothelial cell populations we have established in vitro. These cells have been used in in vitro cytotoxicity experiments to identify and characterize the activated lymphocyte effector cell which we have found to have injurious effects on vascular endothelium. The accessory cell function of vascular endothelium in cellular immune responses has been examined, comparing endothelium from different vessel sources, including microvascular endothelium. We are continuing our studies on the roles played by various leukocyte-derived soluble mediators generated during immune and inflammatory reactions, including interleukin 2 and tumor necrosis factor-alpha, on the growth and function of endothelial cells.
