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

Several products of the activated complement system are known to modulate endothelial cell function in vitro. It has been shown that the membrane attack complex (MAC) (C5b-C9) can enhance turner necrosis factor alpha (TNF-alpha)-induced expression of P- and E-selectin and intercellular adhesion molecule type 1 in cell cultures of human umbilical vein endothelial cells. In the present study the potential role of this synegism for long injury during 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 lipopolysaccharide (LPS) (Escherichia coli O55:B5), we determined the expression of cytokines, chemokines, and adhesion molecules as well as the recruitment of leukocytes in the Lung. Challenge with intraperitoneal i.p. injections of LPS resulted in a strong induction of TNF-alpha, interleukin-1 alpha/beta, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1 alpha and 2, macrophage chemotactic protein 1, and P-selectin. However, there were no significant differences 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-alpha and the MAC of the complement system on the induction of endothelial adhesion molecules is dispensable for inflammatory processes during endotoxin-mediated septic shock in vivo.