Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling
mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo
model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on
plasma EV miRNA profiles.C57Bl/6 mice were total-body irradiated with 0.1 and 2 Gy,
bone marrow-derived EVs were isolated, and injected systemically into naive, 'bystander'
animals. Proteome profiler antibody array membranes were used to detect alterations
in plasma, both in directly irradiated and bystander mice. MiRNA profile of plasma
EVs was determined by PCR array.M-CSF and pentraxin-3 levels were increased in the
blood of directly irradiated and bystander mice both after low and high dose irradiations,
CXCL16 and lipocalin-2 increased after 2 Gy in directly irradiated and bystander mice,
CCL5 and CCL11 changed in bystander mice only. Substantial overlap was found in the
cellular pathways regulated by those miRNAs whose level were altered in EVs isolated
from the plasma of mice irradiated with 0.1 and 2 Gy. Several of these pathways have
already been associated with bystander responses.Low and high dose effects overlapped
both in EV-mediated alterations in signaling pathways leading to RIBE and in their
systemic manifestations.
