Survival of mice with gastrointestinal acute radiation syndrome through control of bacterial translocation

Fujio Suzuki, Bradford D. Loucas, Ichiaki Ito, Akira Asai, Sumihiro Suzuki, Makiko Kobayashi

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Macrophages (Mf) with the M2b phenotype (Pheno2b-Mf) in bacterial translocation sites have been described as cells responsible for the increased susceptibility of mice with gastrointestinal acute radiation syndrome to sepsis caused by gut bacteria. In this study, we tried to reduce the mortality of mice exposed to 7–10 Gy of gamma rays by controlling Pheno2b-Mf polarization in bacterial translocation sites. MicroRNA-222 was induced in association with gamma irradiation. Pheno2b-Mf polarization was promoted and maintained in gamma-irradiated mice through the reduction of a long noncoding RNA growth arrest–specific transcript 5 (a CCL1 gene silencer) influenced by this microRNA. Therefore, the host resistance of 7–9-Gy gamma-irradiated mice to sepsis caused by bacterial translocation was improved after treatment with CCL1 antisense oligodeoxynucleotide. However, the mortality of 10-Gy gamma-irradiated mice was not alleviated by this treatment. The crypts and villi in the ileum of 10-Gy gamma-irradiated mice were severely damaged, but these were markedly improved after transplantation of intestinal lineage cells differentiated from murine embryonic stem cells. All 10-Gy gamma-irradiated mice given both of the oligodeoxynucleotide and intestinal lineage cells survived, whereas all of the same mice given either of them died. These results indicate that high mortality rates of mice irradiated with 7–10 Gy of gamma rays are reducible by depleting CCL1 in combination with the intestinal lineage cell transplantation. These findings support the novel therapeutic possibility of victims who have gastrointestinal acute radiation syndrome for the reduction of their high mortality rates.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalJournal of Immunology
Volume201
Issue number1
DOIs
StatePublished - 1 Jul 2018

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