THE MEMBRANE ATTACK COMPLEX OF COMPLEMENT INDUCES INTERLEUKIN-8 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 SECRETION FROM HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Cell surface assembly of the membrane attack complex (MAC) of compleme nt occurs in a variety of pathophysiological settings, Depending upon the density and size distribution of pores formed by the MAC and the f unctional integrity of membrane regulators of complement activation, t he MAC can either cause direct cell lysis or transduce cell activation . We have examined the functional capacity, of sublytic concentrations of MAC to induce the secretion of specific alpha- and beta-chemokines front human umbilical vein endothelial cells (HUVECs), Endothelial ce ll activation by the MAC has particular relevance to complement-depend ent inflammatory processes including ischemia-reperfusion injury and a cute lung injury, Assembly of sublytic concentrations of the MAC on HU VECs resulted in the sequential secretion of both neutrophil and monoc yte chemotactic activities, Analysis of conditioned medium from MAC-be aring HUVECs revealed that the neutrophil chemotactic activity was lar gely attributable to interleukin (IL)-8, whereas the monocyte chemotac tic activity, which was detected Inter (peak at 8 hours versus 4 hours ), was largely attributable to MCP-1, This temporal pattern of MAC-ind uced secretion of IL-8 and MCP-1 was confirmed using IL-8- and MCP-1-s pecific enzyme-linked immunosorbent assays, Northern hybridization ana lysis of HUVECs revealed that MAC deposition was accompanied by an inc rease in IL-8 and MCP-1 mRNA levels, These data indicate that assembly of sublytic concentrations of the MAC on HUVECs can induce the sequen tial secretion of both neutrophil and monocyte chemotactic activities and that the former is largely attributable to IL-8 whereas the latter is largely attributable to MCP-1.