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.