TY - JOUR
T1 - Endotoxin-induced lung inflammation is independent of the complement membrane attack complex
AU - Brauer, R. B.
AU - Gegenfurtner, C.
AU - Neumann, B.
AU - Stadler, M.
AU - Heidecke, C. D.
AU - Holzmann, B.
PY - 2000
Y1 - 2000
N2 - 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-) (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- 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.
AB - 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-) (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- 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.
UR - http://www.scopus.com/inward/record.url?scp=0033982990&partnerID=8YFLogxK
U2 - 10.1128/IAI.68.3.1626-1632.2000
DO - 10.1128/IAI.68.3.1626-1632.2000
M3 - Article
C2 - 10678982
AN - SCOPUS:0033982990
SN - 0019-9567
VL - 68
SP - 1626
EP - 1632
JO - Infection and Immunity
JF - Infection and Immunity
IS - 3
ER -