STUDIES ON MECHANISM OF ACTION OF GUINEA-PIG LYMPHOTOXIN .1. MEMBRANE ACTIVE SUBSTANCES PREVENT TARGET-CELL LYSIS BY LYMPHOTOXIN

Abstract

Drugs that affect plasma membrane functions interfered with the cytolytic action of LT (lymphotoxin). Dimethyl sulfoxide or lidocaine potentiated [mouse fibroblast] L cell resistance against lysis. Stronger protection was provided by ouabain. Addition of ouabain to cells previously injured by LT was also effective in reducing cell death. Attempts to detect metabolic disturbances in cells before LT cytolysis were unsuccessful. The biosynthetic rate of DNA, RNA or protein, and the total cellular content of ATP were not significantly changed in LT-treated cells. Apparently LT disturbs some plasma membrane functions of the target cell, perhaps ion transport systems, and consequently induces ionic imbalances between the intracellular extracellular milieu which eventually cause cell death.