Ultrastructural evidence of intestinal mucosal macrophage activation after bone marrow transplantation

Abstract

Previous studies have demonstrated upregulation of intestinal mucosal macrophage CD16 (an Fc receptor for IgG) in bone marrow transplant (BMT) recipients with graft-versus-host disease (GVHD). We sought to determine whether there was ultrastructural evidence of mucosal macrophage activation in allogeneic BMT recipients and relate appearances to those seen in autologous BMT patients and to immunohistological findings. Sigmoid colonic mucosal biopsies from five allogeneic and three autologous BMT patients were taken prior to, 30 days after transplant and, in three of the allogeneic patients, 120 days after transplant. These were examined by immunohistochemistry and electron microscopy. Immunohistological analysis revealed upregulation of lamina propria macrophage CD16 after transplant in all patients except one autologous BMT recipient; there were no such changes in total macrophage numbers. Ultrastructural evidence of lamina propria macrophage activation was prominent after both allogeneic and autologous BMT. There was an increase in nuclear size accompanied by increased euchromatin and larger nucleoli. In the cytoplasm there were increased numbers of lysosomes, many of which were small and cylindrical, and cytoplasmic flaps were prominent. Phagosomes were less numerous after transplant. These data confirm that after BMT intestinal mucosal macrophages become activated. However changes in macrophage ultrastructure specific to patients at risk of developing clinical GVHD are lacking.