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Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability

 Kyung Ran Park  ;  Wayne L. Monsky  ;  Chang Geol Lee  ;  Chang Ho Song  ;  Dong Heui Kim  ;  Rakesh K. Jain  ;  Dai Fukumura 
 RADIATION RESEARCH, Vol.185(2) : 182-189, 2016 
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Animals ; Capillary Permeability/physiology* ; Capillary Permeability/radiation effects* ; Dose-Response Relationship, Radiation ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiology ; Endothelium, Vascular/radiation effects ; Mast Cells/physiology* ; Mast Cells/radiation effects* ; Mice ; Mice, Inbred C3H ; Permeability/radiation effects ; Radiation Dosage ; Serum Albumin/metabolism* ; Skin/blood supply ; Skin/metabolism ; Skin/radiation effects ; Skin Physiological Phenomena/radiation effects*
Induction of vascular hyperpermeability is one of the early vascular responses to radiation exposure and is considered to contribute to subsequent fibrosis and tissue injuries. However, the mechanism underlying radiation-induced hyperpermeability has not yet been clearly elucidated. Here, we provide experimental evidence indicating that mast cells contribute to the increase in vascular permeability for albumin in normal mouse skin after irradiation. Vascular permeability in the skin of C3H mice increased after 2, 15 and 50 Gy irradiation, peaked at 24 h after irradiation and gradually decreased thereafter to the baseline level within 3-10 days. Both the extent and duration of hyperpermeability were dose dependent. We found significant degranulation of mast cells in the skin after 15 Gy irradiation. To further investigate the role of mast cells in the radiation-induced increase in vascular permeability, we measured vascular permeability in the skin of mast cell-deficient mice (WW(v)) and their wild-type littermates at 24 h after irradiation. Vascular permeability in WW(v) mice did not change, whereas that in wild-type mice significantly increased after irradiation. There were no appreciable changes in the total tissue levels of vascular endothelial growth factor or endothelial nitric oxide synthase after 15 Gy irradiation and there was no detectable expression of inducible nitric oxide synthase. Collectively, these results show that exposure to radiation induces vascular hyperpermeability in a dose-dependent manner and that mast cells contribute to this process.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
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