The precise role of endothelial cells in inflammation is unknown. However, it is likely that they are important in initiating, sustaining and terminating inflammation by secretion of proinflammatory substances, modulation of immunologically relevant cell surface antigens and receptors and regulation of leukocyte adherence and diapedesis. We have developed techniques to isolate and grow pure cultures of human dermal microvascular endothelial cells (HDMEC) and are conducting an in depth anlaysis of their role in cutaneous inflammation. We also have developed techniques to measure in parallel biologic function (cell adherence) and cell surface expression of immunologically relevant molecules by HDMEC. We have found that these cells express specific cell adhesion molecules on their surface and that these molecules play a critical role in leukocyte endothelial cell adherence reactions. Moreover, we find the expression of these molecules can be upregulated by exposure of the HDMEC's to biologic response modifiers such as IL- l, TNF and IFN-Y. This upregulation is both time and dose responsive and is specific for selected cell adhesion molecules. The substances that stimulate HDMEC are also selective in that they do not upregulate purified human T-cells. Conversely HDMEC are not effected by T cell stimulatory molecules. We have also succeeded in causing HDMEC to undergo rapid differentiation into capillary- like structures by culturing on a matrix known as matrigel. We have defined the key molecule in this complex matrix which acts as the signal for HDMEC angiogenesis. We are investigating the influence of differentiation on the immunological function of HDMEC.
