Comparative studies of the cytotoxic T lymphocyte-mediated cytotoxicity and of extracellular ATP-induced cell lysis. Different requirements in extracellular Mg2+ and pH.

摘要: We recently proposed that extracellular ATP (ATPo) may be involved in CTL-mediated cytotoxicity by acting concert with yet unidentified cellular components (ATPo receptors/ATPo-binding proteins, ectoprotein kinases). The TCR-triggered ATPo accumulation CTL has been demonstrated, whereas the resistance of to was explained action highly active ecto-ATPases or absence relevant ATP-binding proteins. However, no data were available discriminate between possibilities of: i) alone as a "hit" molecule because cell-permeabilizing properties ATP4- ii) "messenger" (as MgATP2-) other molecules. Comparing ATPo-induced and cell lysis, we found lysis some target cells is greatly decreased at neutral acidic pH, Ca(2+)-dependent same barely affected. In agreement observed pH dependency, low Mg2+ concentrations, which favor over MgATP2-, maximal observed. both Ag-specific retargeting assays markedly reduced concentrations. These results suggest cannot fully account for lethal hit delivery very This conclusion further supported studying lytic effect on anti-TCR mAb-coupled SRBC. efficient SRBC detected. not caused high degradation, ecto-ATPase activity much lower than ATPo-resistant OE4 comparable EL4 tumor cells, easily lysed ATPo. suggested need careful consideration cation composition media used effects. caveats use ATP-degrading enzymes implicate role are described here. A clarification previously inhibition hexokinase, an inhibitory salt effect, presented. It if does involve ATP, it function molecules.(ABSTRACT TRUNCATED AT 400 WORDS)