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2014 ; 12
(4
): 238-50
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Radiation-induced impairment in lung lymphatic vasculature
#MMPMID25412238
Cui Y
; Wilder J
; Rietz C
; Gigliotti A
; Tang X
; Shi Y
; Guilmette R
; Wang H
; George G
; Nilo de Magaldi E
; Chu SG
; Doyle-Eisele M
; McDonald JD
; Rosas IO
; El-Chemaly S
Lymphat Res Biol
2014[Dec]; 12
(4
): 238-50
PMID25412238
show ga
BACKGROUND: The lymphatic vasculature has been shown to play important roles in
lung injury and repair, particularly in lung fibrosis. The effects of ionizing
radiation on lung lymphatic vasculature have not been previously reported.
METHODS AND RESULTS: C57Bl/6 mice were immobilized in a lead shield exposing only
the thoracic cavity, and were irradiated with a single dose of 14 Gy. Animals
were sacrificed and lungs collected at different time points (1, 4, 8, and 16
weeks) following radiation. To identify lymphatic vessels in lung tissue
sections, we used antibodies that are specific for lymphatic vessel endothelial
receptor 1 (LYVE-1), a marker of lymphatic endothelial cells (LEC). To evaluate
LEC cell death and oxidative damage, lung tissue sections were stained for LYVE-1
and with TUNEL staining, or 8-oxo-dG respectively. Images were imported into
ImageJ v1.36b and analyzed. Compared to a non-irradiated control group, we
observed a durable and progressive decrease in the density, perimeter, and area
of lymphatic vessels over the study period. The decline in the density of
lymphatic vessels was observed in both subpleural and interstitial lymphatics.
Histopathologically discernible pulmonary fibrosis was not apparent until 16
weeks after irradiation. Furthermore, there was significantly increased LEC
apoptosis and oxidative damage at one week post-irradiation that persisted at 16
weeks. CONCLUSIONS: There is impairment of lymphatic vasculature after a single
dose of ionizing radiation that precedes architectural distortion and fibrosis,
suggesting important roles for the lymphatic circulation in the pathogenesis of
the radiation-induced lung injury.