Complement system is involved in anaphylactoid reaction induced by lipopolysaccharides in muramyldipeptide-treated mice

We previously reported that an intravenous injection of specified bacterial lipopolysaccharides (LPS) induced anaphylactoid shock in muramyldipeptide (MDP)-primed mice of various strains, including LPS-resistant C3H/HeJ, acco mpanied with occasional mortality of mice within 1 h. Prior to shock, rapid accumulation of blood platelets into the lungs and liver followed by degra dation of the platelets and tissue destruction were observed. In this repor t we present the following evidence suggesting that complement activation b y LPS is responsible for the anaphylactoid reaction. In C5-deficient DBA/2 mice, the platelet degradation and anaphylactoid reactions did not occur fo llowing injection of Prevotella intermedia LPS, although transient platelet accumulation into the lungs and liver was observed. Anti-complement agents K-76 COOH (C5 inhibitor) and cobra Venom factor (C5 consumer) protected MD P-primed C3H/HeJ mice from mortality in the anaphylactoid reaction induced by P. intermedia and Salmonella typhimurium LPS, respectively. K-76 COOH al so inhibited platelet degradation, but not accumulation, induced by P. inte rmedia LPS in C3H/HeN mice. LPS specimens carrying mannose-homopolymer (MHP ) prepared from wild-type Klebsiella O3 and Escherichia coli O8 and O9 and recombinant E. coli O8 and O9 strains, which have been reported to markedly activate the human complement system probably through the lectin pathway, induced anaphylactoid reactions in MDP-primed C3H/HeJ mice. In contrast, LP S from R-mutant of Klebsiella O3 and the parental strain of the recombinant E. coil strains, which lacked MHP, did not induce anaphylactoid reaction. Based on these findings together with those of our previous studies, we pos tulated the following mechanism for the anaphylactoid reaction: strong comp lement activation by specified LPS preparations induced degradation of plat elets which have accumulated in the lungs and liver, resulting in acute inf lammation accompanied with severe tissue destruction, especially in the lun gs, which in turn leads to anaphylactoid reaction. However, the mechanism o f platelet accumulation induced by LPS is not yet clear.