ACTIVATION OF THE COMPLEMENT-SYSTEM IN BABOONS CHALLENGED WITH LIVE ESCHERICHIA-COLI - CORRELATION WITH MORTALITY AND EVIDENCE FOR A BIPHASIC ACTIVATION PATTERN

Citation
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
Citations number
42
Categorie Soggetti
Immunology,"Infectious Diseases
Journal title
ISSN journal
00199567
Volume
61
Issue
10
Year of publication
1993
Pages
4293 - 4301
Database
ISI
SICI code
0019-9567(1993)61:10<4293:AOTCIB>2.0.ZU;2-3
Abstract
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.