Lipopolysaccharides as Complement Inhibitors by Complex Formation with the Purified Third Complement Component (C3)

Abstract

Lipopolysaccharides (LPS) from different bacteria in smooth or rough form ( Y. entetocolitice, Y. pseudotuberculosis, E. coli, S. typhirnuriurn, S. rnarcescens) strongly inhibited hemolytic C3 in incubation mixtures with purified C3. LPS from a core deficient mutant was still reactive, whereas lipid A no longer affected C3 activity. The physical state of LPS was critical for its effect on C3. Strand-like LPS structures formed by Ca ++-induced aggregation of solubilized LPS, as shown by electron microscopy, demonstrated the highest reactivity with C3. Inhibition of hemolytic C3 was found to be due to complex formation between LPS and C3 by a hydrophobic reaction. The binding capacity of 1 µg LPS-Rand LPS-S was as high as 125 ng C3 and 56 ng C3, respectively. The C3b fragment required different reaction conditions for maximal binding. The strong binding capacity of L;PS for the complement component C3 raises the possibility that LPS act as inhibitors of complement by interruption of the reaction cascade at local infectious sites with gram-negative bacteria.