Activation of Leukocyte Function-Associated Antigen-1 on Adult T-cell Leukemia Cells

Abstract

Adult T cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium and integrins are tightly regulated by several stimuli such as inflammatory chemokines. We have investigated the mechanisms of extravasation of ATL cells and reported the novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes, and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of PI 3-kinases in an autocrine manner. Furthermore, the cell surface heparan sulfate proteoglycan particularly on ATL cells is involved in chemokine-dependent autocrine stimulation of integrin-triggering by immobilizing the chemokine on them. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.