Changes in vimentin in human macrophages during apoptosis induced by oxidised low density lipoprotein

Macrophage apoptosis contributes to the development of human atheroscleroti c lesions. Oxidised LDL may be involved in macrophage death in vivo. We exa mined morphological and biochemical changes to the vimentin filament networ k during apoptosis of human macrophages. Only oxidised LDL. but not native or acetylated LDL, induced apoptosis, wherein vimentin was cleaved into fra gments of 48-50, 46, 29 and 26 kDa. The use of caspase inhibitors suggested that caspase-6 mediates the formation of the 26 and 46 kDa fragments of vi mentin. We were unable to demonstrate any significant involvement of caspas e-3 in vimentin cleavage. However, caspase-3 was clearly activated during a poptosis whilst caspase-6 expression in macrophages was minimal. Vimentin f ilament breakdown occurred early during apoptosis and vimentin immunoreacti vity was present in apoptotic bodies. However, the application of caspase i nhibitors had no effect on the morphology of the vimentin network in apopto tic cells. suggesting that filament breakdown is not mediated by caspase pr oteolysis. Similar changes in vimentin were also seen in gliotoxin-induced apoptosis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.