SOLUBLE GLUCAN PROTECTS AGAINST ENDOTOXIN-SHOCK IN THE RAT - THE ROLEOF THE SCAVENGER RECEPTOR

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.