Rats received a single intravenous injection with liposome-encapsulated dichloromethylene diphosphonate (C12MDP). This treatment resulted in the elimination of macrophages in spleen and liver within 2 days. Macrophages ingest the liposomes and are destroyed by the drug, which is released from the liposomes after disruption of the phospholipid bilayers under the influence of lysosomal phospholipases. Repopulation of macrophages in spleen and liver was studied at different time intervals after treatment. Macrophages in the liver (Kupffer cells) and red pulp macrophages in the spleen were the first cells to reappear, followed by marginal metallophilic macrophages and marginal-zone macrophages in the spleen. Different markers of the same cell did not reappear simultaneously. On the other hand, the same marker (recognized by the monoclonal antibody ED2) reappeared much more rapidly in the liver than in the spleen. The present results in the rat were different from those earlier obtained in the mouse. Red pulp macrophages were the first cells and marginal zone macrophages were the last cells to repopulate the spleen in both rodents after treatment with C12MDP liposomes. However, there was much more overlap in the repopulation kinetics of splenic macrophage subpopulations in the rat, when compared with the mouse.

We studied the depletion and repopulation of synovial lining cells in mice. A single intra-articular injection of liposomes encapsulating the drug dichloromethylene diphosphonate (CL2MDP) in the mouse knee joint caused selective elimination of synovial lining cells. Depletion of cells occurred within a few days as evidenced by light microscopic, electronmicroscopic and immunohistochemical studies. Maximal depletion was seen on day 7. Repopulation was observed in the following weeks, starting at the bone side of the joint. Until day 30, full recovery (60% recovery) was not observed in the lining lying adjacent to the dermis. Side effects on cartilage metabolism, such as inhibition of proteoglycan synthesis or degradation of proteoglycans from the matrix was minor but significant, 1 and 2 days after liposome treatment but thereafter full recovery was observed. Selective elimination of lining cells from the joint enabled us to study the in vivo role of these cells in the onset and subsequent pathology of experimental arthritis. An immune-complex-mediated experimental arthritis elicited in lining cell depleted joints that had received CL2MDP-liposomes 7 days earlier prevented inflammation as compared to controls.

No abstract

No abstract

Changes occurring in the epithelium covering bronchus-associated lymphoid tissue (BALT) in the rat after several intratracheal administrations of horseradish peroxidase (HRP) were studied using morphological and ultrastructural methods. The epithelium is invaded by W3/25-positive (T-helper) lymphocytes, the BALT epithelial cells become Ia-positive and develop microvilli; there is an apparent loss of cilia. The number of non-ciliated cells in stimulated BALT increases. The non-ciliated cells can be subdivided into two cell types, one with electron-dense cytoplasm and cytoplasmic granules and the other without granules. The electron-density of the latter cell type is intermediate between that of the ciliated cells and that of the granule-containing non-ciliated cells. The granule-containing cell types may be responsible for the uptake of antigens, while the other non-ciliated cell may be involved in the production of the secretory component and the passage of secretory IgA.