Abstract

THE mechanism by which T lymphocytes kill tumour cells is unknown1. The killing is more rapid than reported for lymphotoxin2. Among possible mechanisms are the involvement of complement components3 or phospholipase A, which could generate lysolecithin in the target cell membrane. To test these possibilities we have examined the rates of release from tumour cells of markers of high and low molecular weight and the effects of nonpenetrating solutes. If killing involves disruption of the structure of the cell membrane, for example by lysolecithin, simultaneous release of markers and no protection by macromolecular solutes would be expected. If lysis is osmotic, markers of low molecular weight should be released before those of high molecular weight and nonpenetrating solutes should protect against the lysis by counterbalancing the intracellular osmotic pressure. In the case of complement lysis, small macromolecules of molecular weight less than 40,000, which penetrate through complement lesions, do not inhibit lysis, whereas those of molecular weight above 40,000 protect4.

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