In 3,5,5-trimethylhexanoylferrocene-induced iron overload of rats, three different types of iron-loaded macrophages and derivatives thereof were found in the lungs. On the basis of their localization and of their pattern of iron load it was possible to distinguish: (1) Resident macrophages, showing an alveolar localization and a moderate iron content represented by lysosomal ferritin and haemosiderin. (2) Liver-derived macrophages and giant cells, as well as fragments of them. They showed an exclusive localization in capillaries and alveolar septa, and high concentrations of free ferritin molecules in addition to polymorphous ferritin- and haemosiderin-containing siderosomes. (3) Monocyte-derived intravascular pulmonary macrophages. Initially, they contained iron only as lysosomal aggregates of ferritin and haemosiderin, as a result of phagocytosis of liver-derived macrophageal cell fragments. Later in iron overload, they also showed free ferritin molecules in the cytosol and fused intrapulmonarily to giant cells. The resident as well as the liver-derived siderotic pulmonary macrophages provide a way for iron excretion through the airways.
