INFLAMMATORY MACROPHAGES IN THE DOG CONTAIN HIGH AMOUNTS OF INTRAVESICULAR FERRITIN AND ARE ASSOCIATED WITH POUCHES OF CONNECTIVE-TISSUE FIBERS

We have studied the subcellular distribution of ferritin in inflammatory macrophages present in regional lymph nodes from dogs subjected to a pulmonary inflammatory reaction. The inflammatory reaction was induced by intrabronchial instillation of calcium tungstate (CaWO4), a water‐insoluble powder. Ferritin was identified by electron microscopy, and its electron density was enhanced by the use of a modified Perls method. From day 14 on after the CaWO4 deposition, tungsten‐positive lymph node macrophages showed a massive accumulation of ferritin. Most of the ferritin was stored in membrane‐bounded vesicles that showed heterogeneous concentrations of the protein. A significant complement of ferritin was also detected in the cytoplasmic ground substance of phagocytes. The cell surface of the ferritin‐rich, tungsten‐positive macrophages showed deep infoldings that encompassed small pockets of connective tissue fibers. These features were not observed in control samples or in lymph nodes from dogs subjected to CaWO4‐induced inflammation for periods shorter than 1 week. Our data indicate that inflammatory macrophages greatly increase their content of ferritin and that ferritin is stored predominantly by a membrane‐bounded vesicular compartment. This is in contrast with suggestions that the inflammation‐induced increase in macrophage iron is restricted to the labile pool of iron and it does not involve the iron bound to ferritin molecules. Our observation of nodules of connective‐tissue fibers in intimate topographical association with ferritin‐rich macrophages may indicate that the increase in intracellular ferritin in the macrophage is in some way related to the secretion of factors by the phagocyte that will stimulate fibrillogenesis by neighboring fibroblasts. Copyright © 1991 Wiley‐Liss, Inc.