Irradiation Induces Upregulation of CD31 in Human Endothelial Cells

Abstract

Abstract-Radiation-induced vascular injury is believed to be a major factor contributing to parenchymal atrophy, fibrosis and necrosis in normal tissue after radiotherapy. In this study irradiation of human umbilical vein endothelial cells (HUVECs) significantly increased adherence of U-937 cells in a time-dependent manner. Given the potential multifunctional role of CD31 in the vasculature we have examined the possible effects of irradiation on levels of CD31 expression in HUVECs. Irradiation upregulated CD31 expression on HUVECs, independently of initial plating density and radiation-induced changes such as cell number, cell cycle stage, or cell size. CD31 mRNA levels were raised in irradiated HUVECs relative to controls. Both CD31 mRNA and surface protein showed similar changes, suggesting that the increase in mRNA in irradiated HUVECs is responsible for the elevation in cell surface protein. A semi-quantitative study of tissue specimens from patients who had received radiotherapy indicated that CD31 staining in the blood vessels from irradiated tissues was increased compared with controls. Endothelial CD31 is important in the transmigration of leukocytes. We have demonstrated that the incorporation of monoclonal antibody to CD31 significantly inhibited the transmigration of human peripheral blood leukocytes through a monolayer of irradiated HUVECs. Taken together these data strongly suggest that irradiation induces a marked increase in CD31 expression on endothelial cells as part of a general response to irradiation. Its upregulation may play an important role in the development of radiation-induced normal tissue damage and thus is a possible target for therapeutic intervention. (Arterioscler Thromb Vasc Biol. 1999;19:588-597.)

Low-Dose Ionizing Radiation Stimulates Transcription and Production of Endothelin by Human Vein Endothelial Cells

“…Normal function entails the ability of the vasculature to contract or relax in response to vasoactive hormones and cytokines as well as the ability to form a competent barrier that will resist thrombosis and respond to signals from the immune system. In response to injury or infection, normal endothelial immune response involves altered surface expression of selectins and several other adhesion molecules to facilitate rolling of leukocytes, which, after activation, extravasate where they then function (7,8). Radiation can inappropriately activate this sequence of events, presumably in response to oxidative damage induced at the site (9).…”

Enhancing efficacy of therapeutic vaccinations by combination with other modalities

“…Due to limits in toxicity, some tumor cells within a given tumor mass may receive a sublethal dose of radiation. This dose, however, may be capable of modulating numerous classes of genes, resulting in phenotypic alteration of the tumor cells [4][5][6]. Genes that have been shown to be up-regulated postirradiation in murine and/or human tumors include Fas, MHC class I, ICAM-1, and multiple TAAs.…”

Combining vaccines with conventional therapies for cancer

“…Due to limits in toxicity, some tumor cells within a given tumor mass often receive a sublethal dose of radiation; this dose, however, may modulate numerous classes of genes, resulting in phenotypic alteration of the tumor cells. [4][5][6] Genes that have been shown to be up-regulated postirradiation in murine and/or human tumors include Fas, MHC class I, ICAM-1, and the TAAs CEA, MUC-1, HER-2/neu, p53, and CA125. Up-regulation of any one of these genes can potentially render tumor cells more susceptible to T cell-mediated immune attack.…”