The Activation of Mononuclear Phagocytes: Fact, Fancy, and Future

Abstract Activation revisited. Since the time of Metchinkoff (1) and his contemporaries it has been clear that tissue macrophages exist in various states of activity. One reads about the resting-wandering cells of the connective tissue, arising from the mesenchyme and stimulated by the products of local injury. Such observations performed with the light microscope, vital dyes, and keen insight have in the past two decades been expanded with our increasing knowledge of the mononuclear phagocyte system (2). In the recent past the term “activated macrophage” has largely been relegated to the bactericidal process and to the role of these cells in cell-mediated immunity. Unraveled largely through the imaginative in vivo studies of Mackaness and North and their colleagues (3, 4), the two cell nature of the process, the effector role of the macrophage, and the unique sensitizing qualities of viable organisms were elucidated. Yet, it is apparent when one scans the varied roles of tissue macrophages in the physiology and pathology of mammals that this is a much restricted definition. Although facultative intracellular parasites such as Listeria monocytogenes play a significant role in human morbidity, the basic process of inflammation, tissue remodeling, degradation, and turnover of normal body constituents and antitumor resistance may well be more general expressions of macrophage functions. With these roles in mind I will review some of our newer findings concerning the properties of activated macrophages and the temporal sequence of activation. In certain instances we have a clear understanding of the inducing molecules, in most others we are quite ignorant of both inducer and mechanism. We shall restrict ourselves for the purposes of this discussion to the mouse system and consider as activated properties those of both a qualitative and quantitative nature that exceed the baseline values exhibited by the resident unstimulated peritoneal macrophage. In doing so we will distinguish a group of properties that arise as a result of nonspecific inflammatory factors as opposed to those that require lymphocyte-derived products.