lipid-a and Anaphylaxis

We described the first case reported in literature of anaphylactic shock after administration of pollen extract vaccine chemically modified (allergoid) adsorbed onto L-Tyrosine depot adjuvanted with monophosphoryl lipid A (Pollinex® Quattro MPL-4).

Topics: Anaphylaxis; Humans; Lipid A; Male; Middle Aged; Vaccines

The saccharide constituents of lipopolysaccharides (LPS) of Proteus spp. vary with the strain and contain unique components about which little is known. The biological activities of LPS and lipid A from S- and R-forms of 10 Proteus strains were examined. LPS from all S-form Proteus strains was lethal to D-(+)-galactosamine (GalN)-loaded, LPS-responsive, C3H/HeN mice, but not to LPS-hypo-responsive C3H/HeJ mice. P. vulgaris 025 LPS evoked strong anaphylactoid reactions in N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP)-primed C3H/HeJ mice. LPS from S- and R-form Proteus strains induced production of nitric oxide (NO) and tumour necrosis factor (TNF) by macrophages isolated from C3H/HeN but not C3H/HeJ mice. Lipid A from Proteus strains also induced NO and TNF production, although lipid A was less potent than LPS. The effects of LPS were mainly dependent on CD14; LPS-induced NO and TNF production in CD14+ J774.1 cells was significantly greater than in CD14-J7.DEF.3 cells. All LPS from Proteus strains, and especially from P. vulgaris 025, exhibited higher anti-complementary activity than LPS from Escherichia coli or Pseudomonas aeruginosa. Polymyxin B inactivated proteus LPS in a dose-dependent manner, but these LPS preparations were more resistant to polymyxin B than E. coli LPS. CAP18(109-135), a granulocyte-derived peptide, inhibited proteus LPS endotoxicity only when the LPS:CAP18(109-135) ratio was appropriate, which suggests that CAP18(109-135) acts through a different mechanism than polymyxin B. The results indicate that LPS from Proteus spp. are potently endotoxic, but that the toxicity is different from that of LPS from E. coli or Salmonella spp. and even varies among different Proteus strains. The variation in biological activities among proteus LPS may be due to unique components within the respective LPS.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Amino Acid Sequence; Anaphylaxis; Animals; Antimicrobial Cationic Peptides; Carbohydrate Sequence; Carrier Proteins; Cathelicidins; Complement Inactivator Proteins; Female; Galactosamine; Lipid A; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophage Activation; Male; Mice; Mice, Inbred C3H; Molecular Sequence Data; Nitric Oxide; Peptide Fragments; Polymyxin B; Proteus; Proteus mirabilis; Proteus vulgaris; Tumor Necrosis Factor-alpha

Intravenous injection of muramyl dipeptide (MDP) and Salmonella lipopolysaccharides (LPS) enhanced lethal toxicity of the LPS in C57BL/6 mice. This was true for S (smooth)- and R (rough)-form LPS and free lipid A. Enhancement of toxicity was maximum when the LPS was administered 4 h after MDP, at which time the lethal doses for 50% of mice of S- and R-form LPS and free lipid A were between 1 and 10 micrograms, compared with more than 100 micrograms in normal animals. This sensitization was absent in endotoxin-resistant C3H/HeJ mice. Lethality usually commenced 15 h after LPS injection and was complete after 72 h. Higher doses of some S-form LPS (100 micrograms or more) administered 4 h after MDP led to a strong anaphylactoid reaction within 10 to 20 min of injection, with lethal outcomes in less than 1 h after LPS administration. This early anaphylactoid reaction was observed for various mouse strains, including LPS-resistant C3H/HeJ mice, but it was very weak or completely absent with R-form LPS or free lipid A even in concentrations of up to 1,000 micrograms. A strong anaphylactoid reaction comparable to that seen with S-form LPS was also obtained, after MDP treatment, with an LPS of low toxicity prepared from Bacteroides gingivalis. It is noteworthy that oral administration of MDP also contributed to the anaphylactoid reaction and enhanced the late-phase lethality of LPS. The present findings strongly suggest that the early- and late-phase reactions induced by MDP and LPS are caused by different mechanisms.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Age Factors; Anaphylaxis; Animals; Female; Lipid A; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Sex Factors; Time Factors