Endotoxin-induced lung inflammation is independent of the complement membrane attack complex

Several products of the activated complement system are known to modulate e ndothelial cell function in vitro. It has been shown that the membrane atta ck complex (MAC) (C5b-C9) can enhance turner necrosis factor alpha (TNF-alp ha)-induced expression of P- and E-selectin and intercellular adhesion mole cule type 1 in cell cultures of human umbilical vein endothelial cells. In the present study the potential role of this synegism for long injury durin g endotoxin-mediated septic shock in vivo was examined using a model of C6- deficient PVG (C-) (RT1(C)) rats and the congenic PVG (C+) (RT1(C)) strain. Following administration of a high (5 mg/kg) or low (0.5 mg/kg) dose of li popolysaccharide (LPS) (Escherichia coli O55:B5), we determined the express ion of cytokines, chemokines, and adhesion molecules as well as the recruit ment of leukocytes in the Lung. Challenge with intraperitoneal i.p. injecti ons of LPS resulted in a strong induction of TNF-alpha, interleukin-1 alpha /beta, cytokine-induced neutrophil chemoattractant, interferon-inducible pr otein 10, macrophage inflammatory proteins 1 alpha and 2, macrophage chemot actic protein 1, and P-selectin. However, there were no significant differe nces between PVG (C-) and PVG (C+) rats. Immunoperoxidase staining showed a similar increase of lung infiltration by CD11b/c(+) leukocytes in both rat strains. We therefore conclude that the described synergism between TNF-al pha and the MAC of the complement system on the induction of endothelial ad hesion molecules is dispensable for inflammatory processes during endotoxin -mediated septic shock in vivo.