We have employed an in vitro system to study the interactions between rat serum proteins and lipopolysaccharide (LPS) under conditions similar to those commonly employed in endotoxemia studies. Immediately after mixing, a small fraction of the LPS micelles form a readily precipitable aggregate with serum proteins. Aggregate formation is measurable at LPS concentrations equivalent to maximal serum loads at the lethal threshold in endotoxic shock studies. The amount of aggregate increases with increasing LPS concentration. While the protein content of this aggregate remains stable over the 60 min studied, the LPS content decreases. Only three serum protein species comprise 85-90% of the protein bound in the aggregate: albumin, complement factor C3b and iC3b, and immunoglobulins G and M. Much larger amounts of serum protein-LPS aggregates are formed using serum from animals pre-exposed to sublethal levels of LPS. The results help better characterize the physical-chemical properties of LPS as it is employed in endotoxic shock models in normal and pre-exposed animals and may help explain the altered clearance profiles experienced in these models.
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