Immunologic and nonimmunologic activation of macrophages.

Cells of the mononuclear phagocyte system take on different morphological features and appear to have different functions in immunological and nonimmunological granulomas. In immunological granulomas the appearance is of epitheliod cells. Epitheliod cells are of 2 types. In borderline tuberculoid leprosy granulomas, the appearance is of activated macrophages. Similar activation can be induced by lymphokine which increases respiratory enzyme activity. Other types of epithelioid cell are found in experimental zirconium granulomas. These cells contained rough endoplasmic reticulum, indicating that they may play a secretory role. It is suggested that these cells could play a part in stimulating fibrosis. Other substances that produce nonimmunological granulomas, such as aluminum containing compounds, are directly toxic to macrophages in vitro resulting in the rapid release of cytoplasmic enzymes. These compounds also activate complement, causing C3 conversion and anaphylatoxin production. C3 conversion may be through pathways other than the classical and alternative pathways and does not occur in the absence of plasminogen. Mycobacteria can activate complement through the alternative pathway, suggesting a mechanism for granuloma formation in lepromatous leprosy. Loss of C3 membrane receptors from macrophages in lepromatous leprosy could be produced by feeding peritoneal exudate macrophages with mycobacteria in vitro. This was not just due to phagocytosis, as a similar receptor loss was not obtained when the cells were fed latex particles or zymosan. Epithelioid cells in tuberculoid leprosy and sarcoidosis lose Fc membrane receptors but retain C3 receptors. Thus epithelioid cells can be readily distinguished from other cells of the mononuclear phagocyte series.