Year: 2005
Type: peer-review
Abstract: We describe a method for treating germ-free (GF) mice with ␥-irradiation and transplanting them with normal or genetically manipulated bone marrow while maintaining their GF status.This approach revealed that GF mice are markedly resistant to lethal radiation enteritis.Furthermore, administering lethal doses of total body irradiation to GF mice produces markedly fewer apoptotic endothelial cells and lymphocytes in the mesenchymal cores of their small intestinal villi, compared with conventionally raised animals that have acquired a microbiota from birth.Analysis of GF and conventionally raised Rag1 ؊/؊ mice disclosed that mature lymphocytes are not required for the development of lethal radiation enteritis or the microbiota-associated enhancement of endothelial radiosensitivity.Studies of gnotobiotic knockout mice that lack fasting-induced adipose factor (Fiaf), a fibrinogen͞angiopoietin-like protein normally secreted from the small intestinal villus epithelium and suppressed by the microbiota, showed that Fiaf deficiency results in loss of resistance of villus endothelial and lymphocyte populations to radiation-induced apoptosis.Together, these findings provide insights about the cellular and molecular targets involved in microbial regulation of intestinal radiosensitivity.endothelial cell apoptosis ͉ fasting-induced adipose factor ͉ gnotobiotic knockout and radiation chimeric mice ͉ gut microbiota ͉ radiation enteritis This paper was submitted directly (Track II) to the PNAS office.Freely available online through the PNAS open access option.
Author: Henry Lin
Institution: University of New Mexico
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
Award: G9000045851
OpenAlex ID: W4205790072