Degenerating exo-erythrocytic forms of Plasmodium berghei in rat liver: an ultrastructural and cytochemical study.

Morphological and cytochemical aspects of the host response to almost mature exo-erythrocytic forms (EEF) of Plasmodium berghei in rat hepatocytes were studied by electron microscopy. Young stages (less than 47 h) never evoked a local reaction. Two types of nearly mature EEF (47-51 h) could be distinguished, normal (EEF type I) and those that were the target of infiltrating cells (EEF type II). The latter were in a stage of early or advanced degeneration and generally exhibited increased electron density, especially in the contents of their peripheral vacuoles. Neither type of EEF exhibited detectable enzyme activity, although host cell enzymes, such as peroxidase and 5-nucleotidase, were demonstrable. However, the infected liver cell appeared permeable to ruthenium red whereas non-infected hepatocytes were not. When signs of degeneration were present, as shown by the increasing density of the cytoplasm, loss of enzyme activities occurred. The encompassing mononuclear cells were identified as true monocytes, non-monocyte-derived and monocyte-derived macrophages by their endogenous peroxidase activity. Macrophage filopodia penetrated and cleaved both hepatocyte and parasite cytoplasms. Subsequently, digestion and clearing of the remnants took place. This study clearly demonstrated that a proportion of the intra-hepatocytic EEF was destroyed by macrophages before they were able to mature completely and release their merozoites.