A FUNCTIONAL DEFECT IN HEREDITARY HEMOCHROMATOSIS MONOCYTES AND MONOCYTE-DERIVED MACROPHAGES

Background Hereditary haemochromatosis (HH) is a disease of the metabo lism of iron characterized by increased iron absorption and heavy pare nchymal iron deposition, but with the presence of little iron in the m ononuclear phagocytic system (MPS). Methods To investigate the role of the MPS, the phagocytic ability of HH monocytes (MNs) and in vitro mo nocyte-derived macrophages (MDMs) was studied. HH patients with differ ent degrees of iron accumulation were chosen. Results We observed that HH patients' MNs and MDMs have a significantly decreased ability to p hagocytose rabbit red blood cells (RRBCs) and that HH MNS possess a si gnificantly decreased capacity to phagocytose Staphylococcus aureus (S . aureus). The decrease in the ability to phagocytose S. aureus, howev er, was kinetic in nature, explaining the absence of increased prevale nce of bacterial infections among HH patients. Both RRBCs and S. aureu s were preopsonized with heat-inactivated serum. No alteration in the complement-dependent phagocytosis of Cryptococcus neoformans was demon strated when normal human serum was used. The phagocytosis defect was observed in 100% of HH patients and was independent of the magnitude o f iron overload, age or liver damage, and affected the antibody-mediat ed uptake of bacteria and (R)RBCs.