Intracellular Distribution and Degradation of Bacteriophage in Mammalian Tissues

Abstract

Following i.v. injection into guinea pigs or rabbits, bacteriophages T2 and φX 174 become associated with the large granule fraction of organs with an active reticuloendothelial system. One hour after injection, it was possible to release plaque-forming bacteriophage from the large granule fraction of guinea pig liver by lysing the granules in vitro with lysolecithin, an agent which disrupts membranous organelles. Forty-eight hours after injection of bacteriophage, the absolute number of plaque-forming units within large granules of liver had decreased, but these fractions were more immunogenic than after 1 hr, suggesting that metabolism preceded immunogenicity. Treatment of guinea pigs with excess vitamin A, an agent known to disrupt lysosomes of these large granule fractions, prolonged the 19 S antibody response to bacteriophage φX. Since the duration of the 19 S antibody response is antigen dependent, these findings support the hypothesis that the sequestration and proper degradation of antigens within lysosomes (or phagolysosomes) are necessary steps in the sequence of events leading to antibody formation.