The Clearance, Tissue Distribution, and Cellular Localization of Intravenously Injected Lipopolysaccharide in Rabbits

Abstract The initial interaction of bacterial lipopolysaccharide (LPS) with the blood and tissues of rabbits was studied by using radioiodinated LPS purified from Escherichia coli O111:B4 and Salmonella minnesota R595. After i.v. injection of 250 µg of 125I-LPS, a rapid clearance phase (t1/2 30 min) was observed with substantial uptake of LPS by liver, spleen, and lung during this initial period. With autoradiography, LPS was found to be concentrated in phagocytic vacuoles of hepatic Kupffer cells, splenic macrophages, and leukocytes. LPS remaining in plasma beyond 30 min was converted to a form with a density of less than 1.2 g/cm3, which disappeared from the blood with a half-life of 12 hr. Except for a marked increase in the concentration of O111:B4 LPS in the adrenal glands, tissue-bound LPS concentrations did not change appreciably between 5 and 180 min. When the low density form (ρ 1.2 g/cm3) of either LPS was injected i.v., the initial rapid clearance phase was absent and approximately one-half of the LPS was cleared from blood during the next 4 hr followed by a slower clearance rate (t1/2 = 15 hr). In contrast to findings with the parent LPS, LPS concentrations in the adrenals at 180 min were 3- to 4-fold increased over those in other tissues. Results from SDS-PAGE of LPS recovered from plasma and liver homogenates indicated that no major cleavage of the glycolipid structure of LPS occurred within 180 min. Thus, i.v. injected LPS is rapidly partitioned into tissuebound LPS and that remaining in plasma, neither of which shows evidence of major degradative change within 180 min. Accumulation of low density LPS in the adrenal may compromise the ability of the host to survive in LPS-induced shock.