Specific target cells have been microinjected with cytokines and lymphokines in order to study differences between receptor-mediated signal transduction and direct intracellular introduction of these immunoregulators. Species specificity of interferons for cell surface receptors has been well characterized. However, injected human IFN-gamma was shown to have an intracellular function in mouse macrophages. Microinjection of IFN-gamma induced the expression of Ia antigen on the surface of macrophage cells. The IFN-gamma induced expression of Ia was shown to be mediated by a second messenger, GM-CSF. Microinjection of TNF-alpha has been shown to induce killing of macrophages and fibroblast cells on a dose and time dependent fashion. Certain mutant ras proteins that do not bind GTP were shown to induce DNA synthesis in serum deprived NIH 3T3 cells, suggesting that GTP binding does not necessarily correlate to oncognisity of certain mutant ras proteins. Phospholipase C (PLC), a central enzyme involved in phospholipid metabolism, has been shown to induce DNA synthesis in serum deprived NIH 3T3 cells at catalytic concentrations of protein. This result directly supports the theory that PLC is an important regulator of signal transduction.
