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 Orschell, Louis Pelus

Research output: Contribution to journalArticle

20 Citations (Scopus)

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

Fingerprint

Dinoprostone
Acute Radiation Syndrome
meloxicam
Wounds and Injuries
Hematopoietic System
Stem Cells
Hematopoiesis
Hematopoietic Stem Cells
Mass Casualty Incidents
Nuclear Weapons
Terrorism
Synthetic Prostaglandins
Lymphopenia
Whole-Body Irradiation
Neutropenia
Radio
Thrombocytopenia
Homeostasis
Anti-Inflammatory Agents
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology
  • Cell Biology

Cite this

Hoggatt, J., Singh, P., Stilger, K. N., Plett, P. A., Sampson, C. H., Chua, H. L., ... Pelus, L. (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

Recovery from hematopoietic injury by modulating prostaglandin E2 signaling post-irradiation. / Hoggatt, Jonathan; Singh, Pratibha; Stilger, Kayla N.; Plett, P. Artur; Sampson, Carol H.; Chua, Hui Lin; Orschell, Christie; Pelus, Louis.

In: Blood Cells, Molecules and Diseases, Vol. 50, No. 3, 03.2013, p. 147-153.

Research output: Contribution to journalArticle

Hoggatt, Jonathan ; Singh, Pratibha ; Stilger, Kayla N. ; Plett, P. Artur ; Sampson, Carol H. ; Chua, Hui Lin ; Orschell, Christie ; Pelus, Louis. / Recovery from hematopoietic injury by modulating prostaglandin E2 signaling post-irradiation. In: Blood Cells, Molecules and Diseases. 2013 ; Vol. 50, No. 3. pp. 147-153.
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