Differential sensitivity of two murine leukaemia sublines to cytolysis by Corynebacterium parvum-activated macrophages

摘要

We observed the growth of 2 sublines of leukaemia L1210 in histocompatible DBA2 mice given 10(3) cells i.p. and studied the protective effect of Corynebacterium parvum (CP). The growth of subline L1210-M was unaffected by pretreatment with CP or admixture with 10(5) peritoneal cells (PC) from CP-treated mice. In contrast, the growth of subline L1210-C was inhibited, CP pretreatment increased the proportion of long-term survivors (70% vs 20%) and admixture with CP-PC prolonged the survival time (59 days vs 49 days, P less than 0.05). in vitro experiments indicated that Sublines M and C were equally sensitive to cytostasis by CP-PC, as measured in a terminal labelling assay (greater than 90% inhibition of proliferation). However, subline C was much more sensitive to cytolysis (18h 125IUDR-release assay) by CP-PC; percentage specific release from L1210-C was at least 90%, whilst from L1210-M it was generally less than 25%. The differential susceptibility of the 2 sublines to cytolytic PC was maintained through 75 passages in culture. The effector cells were considered to be macrophages, because they were adherent, phagocytic, and sensitive to silica. Cytolysis was unrelated to endotoxin contamination, because it was not inhibited by polymyxin B, and was inhibited by pre-incubating PC in culture medium for 24 or 48 h before adding target cells. Thus the relevance of nonspecific macrophage-mediated cytotoxicity in vitro to tumour resistance in vivo may depend on the strength of the cytotoxic reaction.