Histopathology of the subchondral bone lesion in rheumatoid arthritis.

Lesions observed in the subchondral marrow of metatarsal and metacarpal heads in advanced rheumatoid arthritis are characterized by proliferation of fibroblasts, deposition of collagen, formation of thin-walled vascular channels, infiltrates of macrophages, lymphocytes and plasma cells, and new bone formation. The overlying hyaline articular cartilage is often necrotic; pannus formation is absent. Although the tissue reaction is basically reparative in nature, aggregates of lymphocytes and plasma cells are also observed around small blood vessels in deeper regions of the bone marrow and may point to a primary bone lesion in this disease.

An electron microscopic study of heme uptake by rat duodenum.

The uptake of heme by mucosal absorptive cells of rat duodenum was studied by electron microscopy; normal and iron-deficient animals were used. Heme was administered as hemoglobin or hemin chloride by means of an intragastric tube and also by injection into a closed duodenal loop. The peroxidatic activity of heme was utilized to locate it on the cell surface and within the cell; aldehyde-fixed mucosal tissue was incubated in a solution of 3,3'-diaminobenzidine. Heme was observed first on the surfaces of the microvilli of the absorptive cell and in apical pits between individual microvilli. Shortly thereafter, heme appeared within membrane-bound tubules which apparently communicated with the apical pits. At later intervals, secondary lysosomes, located in apical cytoplasm and in the supranuclear region of the cell, contained heme; the manner of heme transfer from the apical pit-tubular system to the lysosomal compartment was not defined. Gradual loss, with time, of 3,3'-diaminobenzidine reaction product from secondary lysosomes indicated cleavage of heme therein. Normal and iron-deficient rats handled heme in a similar manner.

Transferrin uptake by rabbit alveolar macrophages in vitro.

Rabbit alveolar macrophages were shown to bind 125I-human transferrin in vitro. The binding reaction was characterized by three stages: (1) adsorption of transferrin to the cells, followed by (2) rapid uptake of the protein to reach (3) a constant level of cell-bound transferrin. The latter two stages were dependent upon temperature and metabolic energy. Macrophages released 125I-transferrin rapidly when incubated with unlabelled transferrin. Small quantities of 125I-rabbit and 125I-bovine serum albumin, by comparison, were bound to and released by the cells; the attachment of these proteins may be solely the result of adsorption. Transferrin, 80% saturated with iron, was bound to a greater extent than 10 or 50% saturated transferrin; 10% saturated transferrin was bound more readily than the 50% saturated preparation. The findings are consistent with the presence of a transferrin receptor on the cell membrane of the alveolar macrophage and imply that transferrin may interact directly with this cell type in order to remove or donate iron.

Two microsomal-associated iron-binding proteins observed in rat small intestinal cells during iron absorption.

Acrylamide gel electrophoresis of microsomal protein obtained from rat small intestinal mucosal cells, after an injection of [3H]leucine, demonstrated increased quantities of two soluble iron-binding proteins during iron absorption, one with a high molecular weight (about 400 000) and the other of intermediate molecular weight (80 000). Both proteins were present in a ribosomal-enriched sub-fraction obtained during purification of the microsomal membrane but were not identified among the purified membrane proteins.

Effect of iron absorption on plasma membrane proteins of small intestinal mucosal cells from iron-deficient rats.

Plasma membrane protein was isolated from small intestinal mucosal cells of normal and iron-deficient rats during iron absorption and examined by acrylamide gel electrophoresis. Two proteins were present in increased amounts in the iron-deficient animals 10 min after administration of iron; uptake studies with 3H-leucine indicated that each had been newly-synthesized. The molecular weights of the proteins were about 60,000 and 300,000.