Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide

Hiromi Funayama, Ling Huang, Tadasu Sato, Yuko Ohtaki, Yoshinobu Asada, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1518-1524
Number of pages7
JournalInternational Immunopharmacology
Volume9
Issue number13-14
DOIs
Publication statusPublished - 2009 Dec

Keywords

  • Complements
  • Lipopolysaccharide
  • Mannan
  • Platelet
  • Platelet-activating factor
  • Shock

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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