Soluble glucan protects against endotoxin shock in the rat: the role of the scavenger receptor.
Soluble carboxymethyl-b-1,3-glucan (CMG), a possible ligand for scavenger receptors, has macrophage-activating action but lacks the granulomatose inflammatory side effect: it is a promising immunomodulator that may mitigate the severity of sepsis. This motivated us to study in rats 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 chemiluminescence of PMNs and macrophages, and on macrophagal tumor necrosis factor (TNF) production. Acetylated low density lipoprotein (AcLDL) clearance in vivo and in vitro binding to macrophages was used to study scavenger receptor function. In the nonpretreated group 9 of 10 rats 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 macrophages and PMNs from CMG-pretreated rats was about two times less (p < .05) than that from nonpretreated ones; the endotoxin induced TNF production by macrophages also decreased. Pretreatment with CMG increased, but coinjection of CMG and AcLDL decreased the AcLDL clearance, while coinjection of endotoxin and AcLDL decreased the survival rate. In vitro AcLDL uptake by macrophages decreased after coinjection with CMG. Our results thus showed that CMG was protective in rat endotoxin shock, which seemed partly connected with enhancement of endotoxin clearance through scavenger receptors and to decreased TNF production.
Vereschagin
E I
EI
Medical Institute, Novosibirsk, Russia.
van Lambalgen
A A
AA
Dushkin
M I
MI
Schwartz
Y S
YS
Polyakov
L
L
Heemskerk
A
A
Huisman
E
E
Thijs
L G
LG
van den Bos
G C
GC
D000818:Animals; D005936:Glucans / Q000494:pharmacology*; D006439:Hemodynamics; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D047071:beta-Glucans
D005936:Glucans; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014409:Tumor Necrosis Factor-alpha; C032629:acetyl-LDL; D047071:beta-Glucans; C029933:carboxymethyl-beta-1,3-glucan