H2S protects against fatal myelosuppression by promoting the generation of megakaryocytes/platelets

J Hematol Oncol. 2016 Feb 24:9:13. doi: 10.1186/s13045-016-0244-7.

Abstract

Background: Our previous pilot studies aimed to examine the role of hydrogen sulfide (H2S) in the generation of endothelial progenitor cells led to an unexpected result, i.e., H2S promoted the differentiation of certain hematopoietic stem/progenitor cells in the bone marrow. This gave rise to an idea that H2S might promote hematopoiesis.

Methods: To test this idea, a mice model of myelosuppression and cultured fetal liver cells were used to examine the role of H2S in hematopoiesis.

Results: H2S promoted the generation of megakaryocytes, increased platelet levels, ameliorate entorrhagia, and improved survival. These H2S effects were blocked in both in vivo and in vitro models with thrombopoietin (TPO) receptor knockout mice (c-mpl(-/-) mice). In contrast, H2S promoted megakaryocytes/platelets generation in both in vivo and in vitro models with TPO knockout mice (TPO(-/-) mice).

Conclusions: H2S is a novel promoter for megakaryopoiesis by acting on the TPO receptors but not TPO to generate megakaryocytes/platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / radiation effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / radiation effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fetus / cytology
  • Hematopoiesis / drug effects*
  • Hematopoiesis / genetics
  • Hematopoiesis / radiation effects
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / radiation effects
  • Hydrogen Sulfide / pharmacology*
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism
  • Megakaryocytes / drug effects*
  • Megakaryocytes / metabolism
  • Megakaryocytes / radiation effects
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Receptors, Thrombopoietin / genetics
  • Receptors, Thrombopoietin / metabolism
  • Sulfides / pharmacology
  • Survival Analysis
  • Thrombopoietin / genetics
  • Thrombopoietin / metabolism
  • Thrombopoietin / pharmacology

Substances

  • Receptors, Thrombopoietin
  • Sulfides
  • Thrombopoietin
  • sodium bisulfide
  • Hydrogen Sulfide