Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide.
Intravenous injection of lipopolysaccharide (LPS, a component of the Gram-negative bacterial cell-surface) or mannan (Man, a component of the fungal cell-surface) into mice reportedly induces anaphylaxis-like shock (ALS) via complement-associated platelet degradation and platelet-activating factor (PAF), respectively. However, it is unclear whether PAF is involved in LPS-ALS or whether complements and/or platelets are involved in Man-ALS. Here, using preparations of Man from Saccharomyces cerevisiae and LPS from Klebsiella O3, we characterized and compared LPS-ALS and Man-ALS, with the following results. (1) ALS depended on mouse strain (ddY and BALB/c being highly responsive to Man and LPS, respectively), but not on Toll-like receptors 2 and 4. (2) In ddY mice, Man had little effect on platelets, K76 (C5a-inhibitor) did not prevent Man-ALS, and Man-ALS was augmented by prior platelet depletion. (3) CV-3988 (PAF antagonist) prevented Man-ALS, but not LPS-ALS. (4) LPS-ALS and Man-ALS were each augmented by prior injection of a muramyl dipeptide (MDP, a constituent abundant in the Gram-positive bacterial cell-surface), but prevented by prior macrophage depletion. (5) Co-administration of Man and LPS induced an augmented ALS in both ddY and BALB/c mice. These results indicate that (i) Man and LPS each induces ALS in mice in strain-dependent and macrophage-dependent (but not TLR-dependent) ways by stimulating a platelet-non-associated PAF pathway and a platelet-associated complement pathway, respectively, and (ii) these pathways are primed by MDP and exhibit mutually augmenting actions. Man-ALS and LPS-ALS may therefore serve as models for diseases involving augmentation by multiple or mixed infections.
Funayama
Hiromi
H
Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Huang
Ling
L
Sato
Tadasu
T
Ohtaki
Yuko
Y
Asada
Yoshinobu
Y
Yokochi
Takashi
T
Takada
Haruhiko
H
Sugawara
Shunji
S
Endo
Yasuo
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051056:Complement Inactivating Agents / Q000008:administration & dosage; D025461:Feedback, Physiological; D006877:Hydroxamic Acids / Q000008:administration & dosage; D007275:Injections, Intravenous; D007709:Klebsiella / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D008351:Mannans / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010742:Phospholipid Ethers / Q000008:administration & dosage; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics
D000276:Adjuvants, Immunologic; D051056:Complement Inactivating Agents; D006877:Hydroxamic Acids; C043237:Klebsiella O3 lipopolysaccharide; D008070:Lipopolysaccharides; D008351:Mannans; D010742:Phospholipid Ethers; D010975:Platelet Aggregation Inhibitors; D051195:Toll-Like Receptor 2; C003486:2-methyl-3-(4-phenylpiperidino)propionohydroxamic acid hydrochloride; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C037913:CV 3988