Studies on the Mechanism of Action of Guinea Pig Lymphotoxin

Abstract

In the previous paper it was suggested that the primary action of guinea pig lymphotoxin (LT) involved creation of ionic imbalances within the target L cells. The nature of these ionic disturbances is explored in this paper. The exogenous addition of CaCl₂, but not KCl or NaCl, inhibited the cytotoxic action of LT. Cellular uptake rates of ⁴⁵Ca⁺⁺, but not ⁸⁶Rb⁺, increased in LT-damaged L cells. The factor responsible for increasing the ⁴⁵Ca⁺⁺ uptake rate cochromatographed on a hydroxyapatite column with the cytotoxic activity of LT. Ouabain prevented the LT-mediated lysis and, concomitantly, depressed the LT-induced increase of ⁴⁵Ca⁺⁺ uptake rate. The LT-damaged L cells excluded trypan blue to the same extent as the normal cells. The addition of LT to an LT-resistant L cell mutant affected neither the ⁴⁵Ca⁺⁺ uptake rate nor the viability. From these observations, damage to the calcium transport system in the L cell plasma membrane is proposed as a mechanism of LT action.