Critical roles of platelets in lipopolysaccharide-induced lethality: Effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome

Zhiqian Yu, Yuko Ohtaki, Kenzou Kai, Takashi Sasano, Hidetoshi Shimauchi, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Katsuo Kumagai, Yasuo Endo

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Within a few minutes of an intravenous injection of a lipopolysaccharide (LPS) into mice, platelets accumulate, largely in the lung. At higher doses, LPS induces rapid shock (within 10 min), leading to death within 1 h. This type of shock differs from so-called endotoxin shock, in which shock signs and death occur several hours or more later. Here, we found that platelet depletion (by a monoclonal anti-platelet antibody) prevented LPS-induced rapid shock, but increased delayed lethality. In Japan, glycyrrhizin (GL), a compound isolated from licorice, is daily and slowly infused intravenously into chronic hepatitis C patients. A single bolus intravenous injection into mice of GL (200 mg/kg or less) shortly before (or simultaneously with) LPS injection reduced the pulmonary platelet accumulation and the severity of the rapid shock, and prevented death in both the early and later periods. GL itself, at 400 mg/kg, produced no detectable abnormalities in the appearance or activity of mice. Intraperitoneal injection of aspirin or dexamethasone had only marginal effects on LPS-induced platelet responses and lethality. These results suggest that platelets play important roles in the development of both the rapid and delayed types of shock induced by LPS. Although the mechanism by which GL suppresses platelet responses and delayed lethality remains to be clarified, GL might provide a strategy for alleviating the acute respiratory distress syndrome seen in sepsis. Our results may also support the proposal by Cinatl et al. [Cinatl J, Morgenstern B, Bauer G, Chandra P, Ravenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003; 361: 2045-6.] that GL may be an effective drug against severe acute respiratory syndrome.

Original languageEnglish
Pages (from-to)571-580
Number of pages10
JournalInternational Immunopharmacology
Volume5
Issue number3
DOIs
Publication statusPublished - 2005 Mar

Keywords

  • Acute respiratory distress syndrome
  • Glycyrrhizin
  • Lipopolysaccharide
  • Platelets
  • Severe acute respiratory syndrome
  • Shock

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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