title: X-ray-induced P-selectin localization to the lumen of tumor blood vessels.
abstract: P-selectin is a cell adhesion molecule that is sequestered in Weibel-Palade storage reservoirs within the vascular endothelium and alpha granules in platelets. P-selectin is rapidly translocated to the vascular lumen after tissue injury to initiate the adhesion and activation of platelets and leukocytes. We studied the histological pattern of P-selectin expression in irradiated tumor blood vessels. We observed that P-selectin was localized within the endothelium of tumor vessels prior to treatment. At 1-6 h following irradiation, P-selectin was mobilized to the lumen of blood vessels. To determine whether radiation-induced vascular lumen localization of P-selectin was tumor type specific or species specific, we studied tumors in rats, C3H mice, C57BL6 mice, and nude mice. P-selectin localization to the vascular lumen was present in all tumors and all species studied. Irradiated intracranial gliomas showed P-selectin localization to the vascular lumen within 1 h, whereas blood vessels in normal brain showed no P-selectin staining in the endothelium and no localization to the irradiated vascular lumen. Radiation-induced P-selectin localization to the vascular lumen increased in time-dependent manner, until 24 h after irradiation. P-selectin in platelets may account for the time-dependent increase in staining within the vascular lumen after irradiation. We therefore used immunohistochemistry for platelet antigen GP-IIIa to differentiate between endothelial and platelet localization of P-selectin. We found that GP-IIIa staining was not present at 1 h after irradiation, but it increased at 6 and 24 h. P-selectin localization to the vascular lumen at 6-24 h was, in part, associated with platelet aggregation. These findings indicate that radiation-induced P-selectin staining in the vascular lumen of neoplasms is associated with aggregation of platelets. Radiation-induced localization of P-selectin to the vascular lumen is specific to the microvasculature of malignant gliomas and is not present in the blood vessels of the irradiated normal brain.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University, Nashville, Tennessee 37232-5671, USA. dennis.hallahan@mcmail.vanderbilt.edu
authors.forename: D E
authors.initials: DE
authors.lastname: Hallahan
authors.forename: M J
authors.initials: MJ
authors.lastname: Staba-Hogan
authors.forename: S
authors.initials: S
authors.lastname: Virudachalam
authors.forename: A
authors.initials: A
authors.lastname: Kolchinsky
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000532:radiotherapy; D004307:Dose-Response Relationship, Radiation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000528:radiation effects*; D005910:Glioma / Q000098:blood supply* / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D019007:P-Selectin / Q000378:metabolism*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins