Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice

Brian J Leibowitz; Liang Wei; Lin Zhang; Xiaochun Ping; Michael Epperly; Joel Greenberger; Tao Cheng; Jian Yu

doi:10.1038/ncomms4494

Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice

Nat Commun. 2014 Mar 18:5:3494. doi: 10.1038/ncomms4494.

Authors

Brian J Leibowitz¹, Liang Wei¹, Lin Zhang², Xiaochun Ping³, Michael Epperly³, Joel Greenberger³, Tao Cheng⁴, Jian Yu⁵

Affiliations

¹ 1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2].
² Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA.
³ Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
⁴ 1] Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA [2] State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
⁵ 1] Department of Pathology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA [2] Department of Radiation Oncology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Abstract

The role of bone marrow (BM) and BM-derived cells in radiation-induced acute gastrointestinal (GI) syndrome is controversial. Here we use bone marrow transplantation (BMT), total body irradiation (TBI) and abdominal irradiation (ABI) models to demonstrate a very limited, if any, role of BM-derived cells in acute GI injury and recovery. Compared with WT BM recipients, mice receiving BM from radiation-resistant PUMA KO mice show no protection from crypt and villus injury or recovery after 15 or 12 Gy TBI, but have a significant survival benefit at 12 Gy TBI. PUMA KO BM significantly protects donor-derived pan-intestinal haematopoietic (CD45+) and endothelial (CD105+) cells after IR. We further show that PUMA KO BM fails to enhance animal survival or crypt regeneration in radiosensitive p21 KO-recipient mice. These findings clearly separate the effects of radiation on the intestinal epithelium from those on the BM and endothelial cells in dose-dependent acute radiation toxicity.

MeSH terms

Abdomen / radiation effects
Animals
Apoptosis / radiation effects
Apoptosis Regulatory Proteins / deficiency
Apoptosis Regulatory Proteins / genetics
Bone Marrow / metabolism
Bone Marrow / radiation effects*
Bone Marrow Cells / cytology
Bone Marrow Cells / metabolism
Bone Marrow Cells / radiation effects
Bone Marrow Transplantation
Epithelial Cells / cytology
Epithelial Cells / metabolism
Epithelial Cells / radiation effects
Female
Gastrointestinal Diseases / etiology*
Gastrointestinal Diseases / genetics
Gastrointestinal Diseases / metabolism
Gastrointestinal Diseases / physiopathology
Humans
Intestinal Mucosa / cytology
Intestinal Mucosa / metabolism
Intestinal Mucosa / radiation effects
Mice, Inbred C57BL
Mice, Knockout
Radiation Injuries / etiology*
Radiation Injuries / genetics
Radiation Injuries / metabolism
Radiation Injuries / physiopathology
Tumor Suppressor Proteins / deficiency
Tumor Suppressor Proteins / genetics
Whole-Body Irradiation / adverse effects*

Substances

Apoptosis Regulatory Proteins
PUMA protein, mouse
Tumor Suppressor Proteins

Abstract

MeSH terms

Substances

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