ACTIVATION OF THE COMPLEMENT-SYSTEM IN BABOONS CHALLENGED WITH LIVE ESCHERICHIA-COLI - CORRELATION WITH MORTALITY AND EVIDENCE FOR A BIPHASIC ACTIVATION PATTERN
Jp. Deboer et al., ACTIVATION OF THE COMPLEMENT-SYSTEM IN BABOONS CHALLENGED WITH LIVE ESCHERICHIA-COLI - CORRELATION WITH MORTALITY AND EVIDENCE FOR A BIPHASIC ACTIVATION PATTERN, Infection and immunity, 61(10), 1993, pp. 4293-4301
Activation of the complement system was studied in baboons that were c
hallenged with live Escherichia coli. In the group challenged with a l
ethal dose (n = 4), the complement activation parameters C3b/c, C4b/c,
and C5b-9 increased 13, 5, and 12 times the baseline value, respectiv
ely, during the first 6 h after the E. coli infusion, whereas in the g
roup challenged with a sublethal dose (n = 10), they increased only mo
derately, by 2 to 3 times the baseline value. However, in this latter
group, a more pronounced activation occurred at 24 h. Subsequent exper
iments showed that this second phase in complement activation started
at 6 h after the challenge, at which time infused microorganisms had b
een cleared from the circulation. The simultaneous increase in C-react
ive protein with this second phase suggested an endogenous activation
mechanism involving this acute-phase protein. Levels of inactivated (m
odified) 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, activati
on of complement in this animal model for sepsis occurs in a biphasic
pattern, the initial phase mediated by the bacteria and the later phas
e mediated by an endogenous mechanism possibly involving C-reactive pr
otein. The differences in complement activation between animals with l
ethal or sublethal sepsis support the hypothesis that complement activ
ation contributes to the lethal complications of sepsis.