Recovery from hematopoietic injury by modulating prostaglandin E2 signaling post-irradiation

Jonathan Hoggatt, Pratibha Singh, Kayla N. Stilger, P. Artur Plett, Carol H. Sampson, Hui Lin Chua, Christie M. Orschell, Louis M. Pelus

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

While high dose total body irradiation (TBI) is used therapeutically, the proliferation of nuclear weapons, increasing use of nuclear power, and worldwide radical terrorism underscore the need to develop countermeasures to a radiological mass casualty event. The hematopoietic syndrome of the acute radiation syndrome (HS-ARS) results from severe compromise to the hematopoietic system, including lymphocytopenia, neutropenia, thrombocytopenia, and possible death from infection and/or hemorrhage. Given adequate time to recover, expand, and appropriately differentiate, bone marrow hematopoietic stem cells (HSC) and progenitor cells (HPC) may overcome HS-ARS and restore homeostasis of the hematopoietic system. Prostaglandin E2 (PGE2) has been shown to have pleiotropic effects on hematopoiesis, acting to inhibit apoptosis and promote self-renewal of HSC, while inhibiting HPC proliferation. We assessed the radio-mitigating potential of modulating PGE2 signaling in a mouse model of HS-ARS. Treatment with the PGE2 analog 16,16 dimethyl PGE2 (dmPGE2) 6h post-irradiation or inhibition of PGE2 synthesis via delayed administration of the non-steroidal anti-inflammatory drug (NSAID) Meloxicam resulted in increased survival of lethally irradiated mice. Both early dmPGE2 and delayed Meloxicam treatment were associated with increased HPC activity 35days following irradiation, demonstrating enhanced recovery of hematopoiesis. Our results define two different treatment modalities that are highly effective and safe to administer, and can be readily available.

Original languageEnglish (US)
Pages (from-to)147-153
Number of pages7
JournalBlood Cells, Molecules, and Diseases
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • Hematopoietic stem cell
  • HS-ARS
  • NSAID
  • Prostaglandin E
  • Radiation

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology
  • Cell Biology

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  • Cite this

    Hoggatt, J., Singh, P., Stilger, K. N., Plett, P. A., Sampson, C. H., Chua, H. L., Orschell, C. M., & Pelus, L. M. (2013). Recovery from hematopoietic injury by modulating prostaglandin E2 signaling post-irradiation. Blood Cells, Molecules, and Diseases, 50(3), 147-153. https://doi.org/10.1016/j.bcmd.2012.11.006