Sequential responses of cultured macrophages to FC loading. In the initial, adaptive phase, CT is activated, leading to increased PC biosynthesis and PC mass and resulting in a normalization of the FC/phospholipid ratio. In addition, there is an increase in the degree of unsaturation of phospholipid fatty acids (FAs). With continued FC loading, death ensues by both apoptotic and necrotic processes. Apoptosis involves both activation of Fas ligand and release of cytochrome c (cyto c) from mitochondria, which may be related to the increased levels of mitochondria-associated Bax in FC-loaded macrophages. FC-induced mitochondrial dysfunction also leads to depletion of cellular ATP stores, which could trigger cellular necrosis.