Resistance against the membrane attack complex of complement induced in porcine endothelial cells with a gal alpha(1-3)gal binding lectin: Up-regulation of CD59 expression

Endothelial cells (EC) play central roles in vascular physiology and pathop hysiology. EC activation results in proinflammatory activities with product ion of cytokines and expression of adhesion molecules. However, we have sho wn before in a model of xenotransplantation that prolonged stimulation of p orcine EC with human anti-porcine IgM natural Abs ran activate the cells to become resistant against cytotoxicity by the membrane attack complex of co mplement (MAC). Now we report the major characteristics of induction and ma intenance of resistance elicited in porcine EC with Bandeiraea simplicifoli a lectin that binds terminal gal alpha(1-3)gal. Lectin-treated cells underw ent little or no cytotoxicity and PGI, release when exposed to MAC. Inducti on of resistance required incubation of the EC with lectin for 4 h but was not fully manifested until 16 h later. Most of the initially bound lectin r emained on the cell surface for >60 h, EC-bound lectin did not inhibit bind ing of IgM natural Abs or activation and binding of C components, including C9, but a C-induced permeability channel of reduced size was present. Indu ction of resistance required protein synthesis, developed slowly, and was a ssociated with up-regulation of expression of mRNA for the MAC inhibitor CD 59 and membrane-associated CD59 protein. Resistance lasted at least 3 days, and the cells regained normal morphology and were metabolically active. Th is induced resistance may have a physiologic counterpart that might be amen able to pharmacologic manipulation in vascular endothelium pathophysiology.