Genetic Control of Macrophage Functions

Macrophages play an important role in various biological phenomena, such as immunoresponsiveness (1-3), nonspecific defence against infections or tumors (4-10), and lipid metabolism (11, 12) . Macrophages are characterized by powerful phagocytic activity and the complex enzyme equipment of their lysozomes . These cells have been grouped by Aschoff and Kiyono in the reticuloendothelial system (RES) .' The phagocytic activity of the group of RE macrophages, in contact with the circulating blood, can be measured from the rate of blood clearance of colloidal carbon particles injected intravenously (13, 14) . The majority (about 90%) of those macrophages are located in both liver and spleen . The basic phagocytic activity of this group of macrophages is fairly constant in different animal species when corrected by the relative mass of liver and spleen (15) . Small variations of the phagocytic activity of RE macrophages have been observed in different inbred strains of mice (6, 16) . Recent observations have demonstrated that these small variations are submitted to genetic control (17) . The phagocytic activity of RE macrophages can be strongly activated by administering different bacteria or bacterial products (4, 5, 10, 18-20), lipid emulsions (21, 22), and hormones (23, 24), Among bacteria, Mycobacterium tuberculosis (BCG strain) and certain corynebacteria (C . paruum) are the most active in stimulating RE macrophages. Responsiveness of macrophages to C. paruum and BCG is submitted to genetic control (20) . Nevertheless, an attempt to separate "high" and "low" lines of mice for the character "macrophage responsiveness to BCG" was unsuccessful (16) . On the contrary, it was possible to separate, by selective breeding, high and low responder lines of mice to the stimulatory effect of glyceryl trioleate (triolein) . Preliminary results of this selective breeding experiment, carried out on eight consecutive generations, have already been reported (20) .