Activation of the complement system in baboons challenged with live Escherichia coli: correlation with mortality and evidence for a biphasic activation pattern.
Activation of the complement system was studied in baboons that were challenged with live Escherichia coli. In the group challenged with a lethal dose (n = 4), the complement activation parameters C3b/c, C4b/c, and C5b-9 increased 13, 5, and 12 times the baseline value, respectively, during the first 6 h after the E. coli infusion, whereas in the group challenged with a sublethal dose (n = 10), they increased only moderately, by 2 to 3 times the baseline value. However, in this latter group, a more pronounced activation occurred at 24 h. Subsequent experiments showed that this second phase in complement activation started at 6 h after the challenge, at which time infused microorganisms had been cleared from the circulation. The simultaneous increase in C-reactive protein with this second phase suggested an endogenous activation mechanism involving this acute-phase protein. Levels of inactivated (modified) C1 inhibitor also increased in both groups, with peak levels of 2.5 times the baseline value at 24 h in the sublethal group and of 4 times at 6 h after the challenge in the lethal group. Thus, activation of complement in this animal model for sepsis occurs in a biphasic pattern, the initial phase mediated by the bacteria and the later phase mediated by an endogenous mechanism possibly involving C-reactive protein. The differences in complement activation between animals with lethal or sublethal sepsis support the hypothesis that complement activation contributes to the lethal complications of sepsis.
de Boer
J P
JP
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Creasey
A A
AA
Chang
A
A
Roem
D
D
Eerenberg
A J
AJ
Hack
C E
CE
Taylor
F B
FB
D000818:Animals; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D010215:Papio; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D003174:Complement C1 Inactivator Proteins; D000515:alpha 1-Antitrypsin; D003179:Complement C3b; D015935:Complement C4b; D010196:Pancreatic Elastase