Endotoxin-Induced Lung Inflammation Is Independent of the Complement Membrane Attack Complex

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Abstract
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 tumor necrosis factor alpha (TNF-α)-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 lung injury during endotoxin-mediated septic shock in vivo was examined using a model of C6-deficient PVG (C−) (RT1C) rats and the congenic PVG (C+) (RT1C) strain. Following administration of a high (5 mg/kg) or low (0.5 mg/kg) dose of lipopolysaccharide (LPS) (Escherichia coliO55: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-α, interleukin-1α/β, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1α 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-α 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.