Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are replaced by proliferating sinusoidal cells in situ to maintain the vascular niche following lethal irradiation

Experimental Hematology
Xiao-Miao LiWilliam B Slayton

Abstract

Bone marrow sinusoids remain predominantly host-derived following bone marrow transplantation. Systematic analysis was conducted at the cellular level to investigate how the host sinusoidal structures survived after lethal irradiation. Apoptosis and cell proliferation assays were performed on bone marrow sections at various time points during the first 2 weeks postirradiation to study the extent of damage to sinusoidal endothelial cells from lethal irradiation and to determine whether cell proliferation contributes to the recovery of the sinusoidal system. Phosphorylated H2AX was present in both hematopoietic and sinusoidal endothelial cells 3 hours after irradiation demonstrating DNA damage. Three days after irradiation, some sinusoidal endothelial cells became terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling -positive, but were caspase-3 and in situ oligo ligation -negative, suggesting nonapoptotic DNA fragmentation. Clusters of sinusoidal endothelial cells that expressed Ki67 appeared 3 days after irradiation, and increased through day 7. These Ki67-positive endothelial cells were host-derived. Bromodeoxyuridine-positive endothelial cells were present in the Ki67-positive areas confirming endothelial cel...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis