THE DISTRIBUTION OF LIPOPOLYSACCHARIDE IN NORMOCOMPLEMENTEMIC AND C3-DEPLETED RABBITS AND RHESUS-MONKEYS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 101  (2) , 245-+
Abstract
To examine the role of complement component 3 (C3) in determining the fate of lipopolysaccharide (LPS) in vivo, the distribution of LPS was studied in normocomplementemic (NC) and C3-depleted animals (pretreated with cobra venom factor [CoF]) after i.v. injection of highly purified, radioiodinated Salmonella minnesota R595 LPS. After injection of a lethal (250 .mu.g) or nonlethal (5 .mu.g) dose of LPS in NC and CoF rabbits and a lethal (5 mg/kg) dose of LPS in rhesus monkeys, the LPS disappeared from blood in a biphasic manner. In all cases, a substantial portion of the dose was removed from blood in an initial disappearance phase (t1/2 [half-life] < 15 min), which, in some cases, was accelerated in CoF-treated animals. LPS remaining in blood beyond 30 min persisted with a much increased t1/2 (> 5 h). Liver contained the major portion (40%) of tissue-bound LPS (determined by use of 131I-BSA [bovine serum albumin] blood marker) in animals killed 3-5 h after injection. The distribution of LPS in rabbits was dose-independent and only minimally changed by prior depletion of C3. The tissue distribution and cellular localization of LPS in monkeys was similar to that reported previously for R595 LPS in NC rabbits, and was not substantially changed by prior CoF treatment. Binding of C3 to i.v. injected LPS apparently is not required for the initial rapid disappearance from blood. The uptake of LPS by cellular targets, notably the hepatic macrophages (Kupffer cells), is not altered by in vivo decomplementation.