Modulation of intercellular communication mediated at the cell surface and on extracellular, plasma membrane–derived vesicles by ionizing radiation  Joseph Albanese, Nicholas Dainiak  Experimental Hematology  Volume 31, Issue 6, Pages 455-464 (June 2003) DOI: 10.1016/S0301-472X(03)00050-X

Figure 1 Plasma membrane damage results from lipid peroxidation. Lipid peroxidation is initiated by a hydroxyl radical, which abstracts a hydrogen atom from polyunsaturated lipid molecules (lipid). This generates a lipid radical, where electron shuffling leads to the formation of conjugated lipid radicals. Molecular oxygen adds to the conjugated lipid radical to form a lipid peroxyl which, in turn, abstracts a hydrogen atom from a nearby lipid molecule to produce a lipid hydroperoxide molecule, while regenerating the lipid radical. This lipid radical can react with another lipid molecule and begin the cycle again. Hence the hydroxyl radical initiates a reaction which is self-perpetuating and results in the oxidative deterioration of polyunsaturated lipid molecules [12]. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 2 Biophysical alterations of the plasma membrane induced by IR. (See text for details.) Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 3 SVs collected from lymphocytes and examined under freeze-fracture electron microscopy. Vesicles in panel A exhibit protrusions that are believed to be integral proteins. In contrast, SVs in panel B are smooth, indicating an absence of transmembrane proteins. Transmission electron microscopy reveals that SVs lack cytoplasmic organelle. Reproduced with permission [50,58]. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 4 Cumulative shedding from irradiated (0.5 Gy) and nonirradiated (control) T lymphocytes. Cells exposed to IR shed significantly less protein in association with SVs, relative to control cells. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 5 TNFSF6-bearing SVs (alone) induce cell death in TNFSF6-sensitive Jurkat cells. Pretreatment with anti-TNFSF6 antibody (Anti-FasL Ab) partially inhibits SV-mediated apoptosis. Jurkat cells treated with CHO SVs or Anti-TNFRSF6 antibody (Anti-Fas) served as negative and positive controls, respectively. Reproduced with permission [42]. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 6 T lymphocytes treated with staurosporine (A), a PKC inhibitor, show a significant reduction in rate of shedding, compared to untreated (control) cells. In contrast, PMA (B), a PKC activator, increases the rate of shedding in lymphocytes. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 7 Irradiated colon cancer cells (SW620) exhibit a dose-dependent increase in TNFSF6 mRNA transcription. Reproduced with permission [42]. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)

Figure 8 Colon cancer cells (SW620) treated with IR (4 and 10 Gy) release SVs with significantly less apoptotic activity, relative to nonirradiated cells (0 Gy). SVs from CHO cells and anti-TNFRSF6 antibody (Anti-Fas) served as negative and positive controls, respectively. Reproduced with permission [42]. Experimental Hematology 2003 31, 455-464DOI: (10.1016/S0301-472X(03)00050-X)