Injury of neoplastic cells by XXXX macrophages leads to inhibition of mitochondrial respiration.

@entity7787 @entity19 @entity948 @entity843 @entity4626 @entity12015 @entity3913 @entity413 @entity3363 @entity897 @entity2383
Cytotoxic activated macrophages (CM) inhibited the growth of neoplastic L1210 cells in vitro but L1210 cell death was minimal to nonexistent. L1210 cells injured by CM were separated from macrophages and studied in an isolated system. CM-injured L1210 cells had an absolute requirement for @entity413 or another glycolyzable @entity12015 ( @entity3913 or @entity948 ) for at least 40 h after removal from macrophages. If the culture medium lacked sufficient concentration of one of these @entity3363 , CM-injured L1210 cells died within 4 h. Uninjured L1210 cells cultured alone or with peptone-stimulated macrophages had no such requirement and maintained complete viability in hexoseless medium. The @entity12015 requirement of CM-injured L1210 cells could not be fulfilled by other naturally occurring @entity7787 , @entity413 or @entity3913 derivatives, or substrates that can be oxidized by mitochondria. The concentration requirements for @entity413 , @entity3913 , and @entity948 by CM-injured L1210 cells correlated with the concentrations required to support maximal glycolysis of these @entity3363 by other @entity19 @entity843 cells. A concentration of @entity897 which completely inhibited L1210 cell glycolysis also complete prevented the ability of @entity413 or @entity3913 to maintain viability of CM-injured L1210 cells. Interaction with CM led to inhibition of L1210 cell mitochondrial oxidative phosphorylation. This was supported by the findings that: (a) CM-injured L1210 cells had no Pasteur effect; their rate of aerobic glycolysis was the same as the rate of anaerobic glycolysis of uninjured L1210 cells, (b) Endogenous respiration of CM-injured L1210 cells was 15% of normal. Maximal inhibition of uninjured L1210 cell respiration by a specific mitochondrial poison ( @entity4626 ) was nearly the same (13% of normal). It followed that CM-injured L1210 cells required @entity12015 for chemical energy production via the glycolytic pathway. CM-induced @entity2383 occurred in five other neoplastic cell lines tested.
