Soluble carboxymethyl-b-1,3-glucan (CMG), a possible ligand for scaven
ger receptors, has macrophage-activating action but lacks the granulom
atose inflammatory side effect: it is a promising immunomodulator that
may mitigate the severity of sepsis. This motivated us to study in ra
ts the effect of CMG (25 mg/kg), injected into the tail vein at 48 and
24 h prior to the administration of 5 mg/kg Escherichia coli 0127.B8
endotoxin on survival, hemodynamic condition, and, in vitro, on the ch
emiluminescence of PMNs and macrophages, and on macrophagal tumor necr
osis factor (TNF) production. Acetylated low density lipoprotein (AcLD
L) clearance in vivo and in vitro binding to macrophages was used to s
tudy scavenger receptor function. In the nonpretreated group 9 of 10 r
ats died during the first 24 h after endotoxin, but all CMG-pretreated
rats survived. CMG-pretreatment prevented severe decreases in cardiac
output and blood pressure after endotoxin. Chemiluminescence of macro
phages and PMNs from CMG-pretreated rats was about two times less (p <
.05) than that from nonpretreated ones; the endotoxin induced TNF pro
duction by macrophages also decreased. Pretreatment with CMG increased
, but coinjection of CMG and AcLDL decreased the AcLDL clearance, whil
e coinjection of endotoxin and AcLDL decreased the survival rate. In v
itro AcLDL uptake by macrophages decreased after coinjection with CMG.
Our results thus showed that CMG was protective in rat endotoxin shoc
k, which seemed partly connected with enhancement of endotoxin clearan
ce through scavenger receptors and to decreased TNF production.