Activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells

Adult T cell leukemia (ATL) is characterized by massive infiltration of cir culating ATL cells into a variety of tissues, a finding often associated wi th poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium and integrins are tightly reg ulated by several stimuli such as inflammatory chemokines. We have investig ated the mechanisms of extravasation of ATL cells and reported the novel fe atures of endogenous chemokine-induced adhesion of ATL cells to the endothe lium. We propose that ATL cells adhere to endothelial cells through an adhe sion cascade similar to normal leukocytes, and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeleta l rearrangement induced by G-protein-dependent activation of PI 3-kinases i n an autocrine manner. Furthermore, the cell surface heparan sulfate proteo glycan particularly on ATL cells is involved in chemokine-dependent autocri ne 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.