Influence of human anti-lipopolysaccharide immunoglobulins on tissue distribution and clearance of lipopolysaccharide in rats

To examine the influence of passive immunization on the biological fate of injected lipopolysaccharide (LPS), we used a human IgG preparation (anti-LP S IgG) rich in antibodies to a large panel of smooth and rough purified LPS extracts as well as a normal IgG preparation (standard IgG). Our approach was to compare the uptake of I-125-labeled LPS by the tissues of saline or IgC-treated rats. After intravenous injection, one fraction of I-125-labele d Escherichia coli 055:B5 LPS is rapidly taken up by tissues, while another fraction remained in the blood. Uptake of I-125-labeled LPS was principall y observed into the liver and spleen. In rats treated prophylactically with standard IgG, these tissues accumulated significantly larger amount of LPS than the tissues of rats treated with anti-LPS IgG. Nevertheless, both IgG preparations increased the specific binding of LPS by the liver and spleen . High levels of homologous unlabeled LPS decreased the uptake of LPS by th e liver, presumably by occupying tissue receptors, whereas in the presence of E. coli 0127:B8 LPS, an increase of the uptake of I-125-labeled LPS by t he liver and lungs was observed. The pharmacokinetics and tissue distributi on of LPS-IgG complexes pre-formed in vitro were compared. In the presence of standard IgC, a unexpected increase of the uptake of LPS by the tissues was recorded, whereas LPS-anti-LPS IgG complexes decreased the binding of I -125-labeled LPS to the tissues. On the other hand, the vascular effects in duced by LPS did not appear to be modified in rats pretreated with either I gG preparation. In conclusion, although passive immunization against LPS sl ightly modified the uptake and clearance of LPS, neither in vitro nor in vi vo formation of LPS-anti-LPS IgG complexes afforded a very significant prot ection against the toxic effects of LPS.