[Mechanisms of macrophage activation and macrophage-mediated tumoricidal activity]

Macrophages exert important roles in the host defense mechanism, such as antigen presentation and destructions of tumor cells. Analysis of macrophage functions as effector cells in the tumor cell destruction has been carried out mainly from two aspects. One is the macrophage activation, during which macrophages are sequentially activated from resting cells to fully activated cells with capability to destroy tumor cells. The other is analysis of active moieties which mediate macrophage tumoricidal activity. The recombinant cytokines become available, and IFN-gamma has been found to be a major constituent of macrophage activating factor. It has been also reported that TNF, -IL-4, GM-CSF or IL-2 has MAF activity. The precise mechanism of signal transduction of IFN gamma will be defined by the recent progress on IFN gamma receptor purification and gene cloning for IFN gamma receptor as well as on the analysis of IFN gamma-inducible genes. As the mechanism of macrophage-mediated tumoricidal activity, two pathways, TNF-dependent and arginine-dependent ones, have been proposed.