By phase-contrast cinemicroscopy, highly purified human lymphotoxin induced two forms of cytolysis-one characterized by slow (1 to 2 hours) swelling (ballooning-type) and the other by sudden (3 to 5 minutes) shrinkage of the cell body and violent agitation of residual debris (popcorn-type). Specifically sensitized lymphocytes likewise caused both forms of lysis, morphologically indistinguishable from lymphotoxin-induced cytolysis. Lymphotoxin also inhibited cell division; mitoses diminished and virtually ceased before the onset of cytolysis. Many of the ultrastructural features preceding early lysis were similar to those associated with failure of osmoregulatory mechanisms-ie, condensation of mitochondria, dilation of rough-surfaced endoplasmic reticulum, separation of polysomes into individual units and expansion of the cell sap. After exposure to lymphotoxin for 12 hours or more, most remaining cells exhibited these same ultrastructural changes but lacked striking mitochondrial lesions.
Tumor necrosis factor α (TNF-α) is a cytokine with multiple roles in the immune system, including the induction and potentiation of cellular functions in neutrophils (PMNs). TNF...