Genetic and Functional Studies of Continuous Macrophage-Like Cell Lines

Abstract

The mechanisms by which macrophage functions are regulated represent a fascinating area of cell biology because of the wide variety of cellular and immunological activities carried out by these highly differentiated cells, the most significant being phagocytosis, antigen presentation, resistance to intracellular parasites, killing and growth inhibition of tumor cells, and tissue damage. Definition of macrophage functions has been aided in recent years by the careful study of primary, resident or induced murine peritoneal exudate cells exposed to a variety of stimuli and pharmacological agents. There are, however, a number of inherent limitations on the analysis of macrophage functions imposed by the study of primary cells: 1) most sources of primary macrophages are heterogeneous cell populations; 2) primary cell populations contain macrophages at various stages and states of differentiation; and 3) primary macrophages under standard conditions fail to grow in tissue culture. The availability of cloned populations of macrophage-like continuous cell lines offers the possibility to select stable variants and mutants in individual macrophage functions. The goal of these studies is to isolate a variety of mutants in individual macrophage functions, ultimately to permit formulation of an integrated scheme for the complex mechanisms of macrophage functions. In addition, it has recently become possible to construct somatic cell hybrids which retain selected macrophage functions, thus expanding the possibilities for producing continuous macrophage-like cell lines.