Dynamics of platelet behaviors as defenders and guardians: Accumulations in liver, lung, and spleen in mice

Zhiqian Yu, Masahiro Shibazaki, Hirotada Otsuka, Haruhiko Takada, Masanori Nakamura, Yasuo Endo

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Systemic platelet behaviors in experimental animals are often assessed by infusion of isotope-labeled platelets and measuring them under anesthesia. However, such procedures alter, therefore may not reveal, real-life platelet behaviors. 5-Hydroxytryptamine (5HT or serotonin) is present within limited cell-types, including platelets. In our studies, by measuring 5HT as a platelet-marker in non-anesthetized mice, we identified stimulation- and time-dependent accumulations in liver, lung, and/or spleen as important systemic platelet behaviors. For example, intravenous, intraperitoneal, or intragingival injection of lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria), interleukin (IL)-1, or tumor necrosis factor (TNF)-α induced hepatic platelet accumulation (HPA) and platelet translocation into the sinusoidal and perisinusoidal spaces or hepatocytes themselves. These events occurred "within a few hours" of the injection, caused hypoglycemia, and exhibited protective or causal effects on hepatitis. Intravenous injection of larger doses of LPS into normal mice, or intravenous antigen-challenge to sensitized mice, induced pulmonary platelet accumulation (PPA), as well as HPA. These reactions occurred "within a few min" of the LPS injection or antigen challenge and resulted in shock. Intravenous injection of 5HT or a catecholamine induced a rapid PPA "within 6 s." Intravenous LPS injection, within a minute, increased the pulmonary catecholamines that mediate the LPS-induced PPA. Macrophage-depletion from liver and spleen induced "day-scale" splenic platelet accumulation, suggesting the spleen is involved in clearing senescent platelets. These findings indicate the usefulness of 5HT as a marker of platelet behaviors, and provide a basis for a discussion of the roles of platelets as both "defenders" and "guardians".

Original languageEnglish
Pages (from-to)1253-1267
Number of pages15
JournalBiological and Pharmaceutical Bulletin
Volume42
Issue number8
DOIs
Publication statusPublished - 2019

Keywords

  • Liver
  • Lung
  • Platelet
  • Serotonin
  • Spleen
  • Systemic behavior

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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