Modulation of intercellular communication mediated at the cell surface and on extracellular, plasma membrane-derived vesicles by ionizing radiation

The plasma membrane is a dynamic organelle whose function includes receptor-mediated signal transduction into the cell. Conversely, the plasma membrane is the origin of intercellular signaling. In addition to expressing and releasing growth factors in a soluble form (through exocytosis) and via proteolysis of cell surface components, membrane ligands may signal nearby cells through juxtacrine stimulation or by the exfoliation or shedding of plasma membrane-derived vesicles. Ionizing radiation (IR) has a profound effect on plasma membrane structure and function. IR-induced ultrastructural alterations are mediated via lipid interaction with water radiolysis products (e.g., hydroxyl radicals, hydrogen radicals, and hydrated electrons). Ionizing radicals act directly on lipid molecules to promote lipid hydroperoxides and lipid hydroperoxide breakdown products (e.g., alpha, beta unsaturated aldehydes) that contribute to altered plasma membrane lipid composition. A change in lipid composition increases membrane lipid microviscosity and results in membrane fenestrations that enhance permeability to small molecules and ions. Reactive ionizing species also stimulate sphingomyelinase activity, leading to sphingomyelin hydrolysis and ceramide generation that further contributes to altered membrane lipid composition and cellular apoptosis. In addition, exposure to IR results in impaired rate of and cumulative shedding of plasma membrane-associated growth factors. Mechanisms of exfoliation are reviewed for normal cells and the impact of radiation on modulating signal transduction mediated by exfoliation is summarized. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.