Antigen-antibody complexes and soluble mediators of inflammation such as the complement derived anaphylatoxins play important roles in a variety of human systemic and cutaneous diseases. Serum sickness is a prototypical immune complex disease. We have performed the first prospective indepth immunological and immunopathological study of serum sickness in man. We have defined the time course of the clinical, immunological and immunopathological findings in human serum sickness. We have described a hitherto unknown cutaneous sign in humans specific for serum sickness. Since immune complexes may activate the complement system and since the complement fragments C5a and C3a are thought to be important in the pathogenesis of the inflammatory response in cutaneous and systemic diseases, we have purified human C5a and C5a des Arg studied their in vivo and in vitro reactivity. In vivo role was assessed by the first in-depth analyses of the cutaneous reactivity of these complement fragments in man. We have also studied the ability of C5a and C3a to modulate cell surface receptors for immunoglobulin and complement on the surface of leukocytes. Increasing evidence indicates that human endothelial cells, under certain circumstances, can be induced to become immunologically competent. In order to evaluate the role endothelial cells in immune disorders of the skin we have isolated human umbilical vein, grown them in cell culture, examined them for the presence of immunologically relevant cell surface antigens and receptors before and after stimulation with soluble mediators of immunoregulation. In addition we have isolated human dermal microvascular endothelial cells from human foreskins, purified them successfully, passaged them in tissue culture and performed analyses of their immunological phenotypes.
