Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni.

Previous work has shown that cell suspensions from egg granulomas of Schistosoma mansoni-infected mice contain populations of both I-A-positive and -negative granuloma macrophages (GMs). The present study was undertaken to investigate the distribution of I-A-bearing macrophages within the granulomas, as well as the kinetics of I-A antigen expression by these cells in vivo. Cryostat sections of liver tissue from infected animals, stained with monoclonal anti-I-A antibodies, demonstrated the presence of I-A-positive GMs in peripheral areas of the granulomas, whereas I-A-negative cells concentrated in their centers. For investigation of their expression of I-A antigen, dispersed GMs were studied at time intervals after subjecting infected mice to lethal doses of total body irradiation. I-A half-life on GMs in vivo was estimated to be 2 days, based both on visual detection by immunofluorescence and functionally on the ability of GMs to perform as antigen-presenting cells. Autoradiographic studies, performed on infected liver tissue obtained 1 hour after in vivo administration of tritiated thymidine, showed that macrophages predominantly replicated in peripheral areas of the schistosomal egg granulomas. After longer intervals, however, labeled cells were seen in more central areas of the granuloma, suggesting an overall cell flux from the periphery to the center. These findings indicate that macrophages express I-A antigens in peripheral areas of the granulomas, where macrophage replication and recruitment from the bone marrow take place. They suggest that I-A expression occurs during a limited period of time in "young" macrophages, which later may convert to an I-A-negative phenotype.