title: Mast Cells Contribute to Radiation-Induced Vascular Hyperpermeability.
abstract: 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.
authors.affiliation: a  Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Kyung Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: a  Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Monsky
authors.affiliation: a  Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Chang Geol
authors.initials: CG
authors.lastname: Lee
authors.affiliation: b  Department of Anatomy, Chonbuk National University Medical School, Chonju, Republic of Korea; and.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Song
authors.affiliation: c  Department of Basic Science, Institute of Basic Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Dong Heui
authors.initials: DH
authors.lastname: Kim
authors.affiliation: a  Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.affiliation: a  Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumura
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology / Q000528:radiation effects; D008407:Mast Cells / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D010539:Permeability / Q000528:radiation effects; D011829:Radiation Dosage; D012709:Serum Albumin / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000378:metabolism / Q000528:radiation effects; D012879:Skin Physiological Phenomena / Q000528:radiation effects*
chemical_list: D012709:Serum Albumin