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, accompanied with occasional mortality of mice within 1 h. Prior to shock, rapid accumulation of blood platelets into the lungs and liver followed by degradation of the platelets and tissue destruction were observed. In this report we present the following evidence suggesting that complement activation by LPS is responsible for the anaphylactoid reaction. In C5-deficient DBA/2 mice, the platelet degradation and anaphylactoid reactions did not occur following 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 MDP-primed C3H/HeJ mice from mortality in the anaphylactoid reaction induced by P. intermedia and Salmonella typhimurium LPS, respectively. K-76 COOH also inhibited platelet degradation, but not accumulation, induced by P. intermedia LPS in C3H/HeN mice. LPS specimens carrying mannose-homopolymer (MHP) prepared from wild-type Klebsiella 03 and Escherichia coli 08 and 09 and recombinant E. coli 08 and 09 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, LPS from R-mutant of Klebsiella 03 and the parental strain of the recombinant E. coli strains, which lacked MHP, did not induce anaphylactoid reaction. Based on these findings together with those of our previous studies, we postulated the following mechanism for the anaphylactoid reaction: strong complement activation by specified LPS preparations induced degradation of platelets which have accumulated in the lungs and liver, resulting in acute inflammation accompanied with severe tissue destruction, especially in the lungs, which in turn leads to anaphylactoid reaction. However, the mechanism of platelet accumulation induced by LPS is not yet clear.
Kawabata
Y
Y
Department of Microbiology and Immunology, Kagoshima University Dental School, Japan.
Yang
T S
TS
Yokochi
T T
TT
Matsushita
M
M
Fujita
T
T
Shibazaki
M
M
Noikura
T
T
Endo
T Y
TY
Takada
H
H
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000707:Anaphylaxis / Q000097:blood / Q000276:immunology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002240:Carbohydrate Sequence; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007709:Klebsiella; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry; D018713:Prevotella intermedia; D011994:Recombinant Proteins / Q000737:chemistry / Q000633:toxicity; D012486:Salmonella typhimurium; D012717:Sesquiterpenes / Q000494:pharmacology
D003169:Complement Inactivator Proteins; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D011994:Recombinant Proteins; D012717:Sesquiterpenes; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C038797:K 76 carboxylic acid