title: Endotoxin-induced lung inflammation is independent of the complement membrane attack complex.
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-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 lung 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-1alpha/beta, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1alpha 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.
authors.affiliation: Department of Surgery, Immunology and Hygiene, Klinikum rechts der Isar, Technische Universität München, D-81675 Munich, Germany. brauer@nt1.chir.med.tu-muenchen.de
authors.forename: R B
authors.initials: RB
authors.lastname: Brauer
authors.forename: C
authors.initials: C
authors.lastname: Gegenfurtner
authors.forename: B
authors.initials: B
authors.lastname: Neumann
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.forename: C D
authors.initials: CD
authors.lastname: Heidecke
authors.forename: B
authors.initials: B
authors.lastname: Holzmann
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003183:Complement C6 / Q000172:deficiency / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D016177:Macrophage-1 Antigen / Q000502:physiology; D008297:Male; D011014:Pneumonia / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D018925:Chemokines; D003183:Complement C6; D015938:Complement Membrane Attack Complex; D016207:Cytokines; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha