Complement-Mediated Endothelial Cell Damage in Immune Complex Vasculitis of the Skin: Ultrastructural Localization of the Membrane Attack Complex

Abstract

Activation of the complement system is an important element in our concept of the pathomechanism of immune complex (IC) vasculitis. Both deposition of IC and attraction of polymorphonuclear leukocytes (PMN) are effected by products of complement activation. Actual tissue damage, however, is believed to be caused by PMN penetrating the vessel wall. Our former finding that deposits of membrane attack complex of complement (MAC) are found predominantly in skin lesions of patients with IC vasculitis and not in perilesional skin, has raised the question whether the complement system itself (by way of the MAC) contributes to tissue damage. Our present study shows the ultrastructural localization of MAC in lesional and clinically uninvolved skin in two patients with a cutaneous IC vasculitis. Lesional skin deposits of MAC were found on endothelial cells (EC) of upper dermal vessels and on infiltrating PMN. Uninvolved skin deposits of MAC were found on some EC, but clearly to a lesser extent than on EC of the lesional skin. In the skin of two healthy controls MAC was only found sporadically on EC. Deposits of MAC on EC in the lesional skin were often associated with a typical form of local cell swelling. This local form of endothelial cell swelling was incidentally seen in vessels of clinically uninvolved skin, but not in the skin of the two controls. The association of the endothelial cell swelling with deposits of MAC suggests that the complement system can have a direct damaging effect on EC in IC vasculitis by the assembly of MAC on the endothelial cell membrane.