Studies on the Mechanism of Action of Guinea Pig Lymphotoxin. II. Increase of Calcium Uptake Rate in LT-Damaged Target Cells.

摘要

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 Ca 45(++), but not Rb86(+) increased in LT-damaged L cells. The factor responsible for increasing the Ca 45(++) 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 Ca 45(++) 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 Ca 45(++) 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. (Author)