Analysis of bypass activation of C3 by endotoxic LPS and loss of this potency.

Endotoxic lipopolysaccharides prepared from Salmonella minnesota smooth form (LPS-S) and rough form, R 595 (LPS-R) activate C3 in guinea-pig serum as is demonstrated by C3 kinetics and generation of anaphylatoxic activity. The activation depends on the presence of certain serum factors, one of which is the protein (SF) interacting with the cobra venom factor, on the presence of Mg++, the temperature and on dose of LPS applied. This turnover of C3 is terminated at 37° within 2 minutes (LPS-R) to 12 minutes (LPS-S) and then reaches a plateau. The amount of C3 consumption, i.e. the level of the plateau, is typical for given concentrations of LPS-S and LPS-R (intermediate plateau). Above a certain LPS-concentration additional LPS does not induce further C3 turnover (maximal plateau). While the `maximal plateau' may be explained by a limitation of the factors needed for the LPS dependent consumption of C3, the `intermediate plateau' and the termination of the action on C3 are not well understood. It is hypothesized that coating of the LPS molecule by serum protein, e.g. albumin, inactivates LPS-S and LPS-R with regard to their action on C3. C3 and C5 in normal serum concentrations appear not to be involved. It is suggested that an additional mechanism for termination of LPS action is a rapid loss of activity of LPS-induced intermediates.