Irradiation is an early determinant of endothelial injury during hematopoietic stem cell transplantation

Abstract

Objective: We investigated the degree and the time course of endothelial injury in mice pretreated with lethal or reduced-intensity irradiation administered before transplantation.

Materials and methods: Six- to eight-week-old female mice were randomly allocated into three groups: lethal-intensity irradiation (8.5 Gy, group 1), reduced-intensity irradiation (5.0 Gy, group 2), or nonirradiated controls (group 3). After conditioning, circulating endothelial cells (CD31+, CD133(-), and CD45low) and peripheral blood CD4+ or CD8+ T-lymphocyte subpopulations were enumerated using flow cytometry at various times. The morphologic changes in endothelium were examined at phase-contrast light microscopy.

Results: Circulating endothelial cells showed an earlier and higher peak in the lethal irradiation group compared with the reduced-intensity irradiation group, which exhibited a protean elevation in cell numbers. There were no visible histopathologic changes during the early stage of endothelial damage.

Conclusions: Lethal and reduced doses of irradiation induced endothelial injury in a dose-dependent manner. Endothelial damage may occur before graft-vs-host disease and its related complications.