Emperipolesis describes a cellular event where one living cell actively enters and moves within the cytoplasm of another living cell. Derived from Greek words meaning “inside” and “to wander about,” this phenomenon involves active penetration without the internalized cell being digested. It represents a unique interaction in cellular biology.
What is Emperipolesis?
Emperipolesis involves a living cell, such as a lymphocyte, plasma cell, or erythrocyte, entering and actively moving within the cytoplasm of a larger host cell, often a megakaryocyte or histiocyte. A defining characteristic is that both the internalized cell and the host cell remain viable and intact throughout the process.
Unlike other cellular uptake mechanisms, the internalized cell is not destroyed by lysosomal enzymes. This process can be observed through microscopy, where the internalized cell appears within a clear halo or membrane-bound vacuole. The internalized cell can move freely and even exit the host cell without causing damage to either cell, highlighting its distinct nature.
The cells most commonly observed undergoing emperipolesis are hematopoietic cells like neutrophils, lymphocytes, and plasma cells, found within host cells such as megakaryocytes or histiocytes. Megakaryocytes, large cells in the bone marrow responsible for platelet production, frequently show this phenomenon. Other host cells can include monocytes, endothelial cells, fibroblasts, and even malignant cells.
Emperipolesis: A Unique Cellular Interaction
Emperipolesis stands apart from other cellular processes, primarily due to the viability and active movement of the internalized cell. Phagocytosis, for instance, involves an engulfing cell, typically a macrophage, consuming foreign particles, dead cells, or cellular debris. In phagocytosis, the engulfed material is subsequently digested and destroyed by lysosomal enzymes within the host cell.
Endocytosis is a broader process where cells take in molecules or particles from outside by forming vesicles. This differs from emperipolesis, which involves the active entry and movement of an entire living cell within another. While endocytosis involves membrane invagination, emperipolesis involves a whole cell entering another.
Emperitaxis refers to the active migration of cells, such as lymphocytes, through tissues or between cells, often in response to chemical signals, describing movement across a cellular barrier or through extracellular spaces. Emperipolesis, however, denotes the active penetration and movement within the cytoplasm of another cell, emphasizing intracellular localization rather than transmigration through tissue. It involves the active cytoskeletal participation of both the host and guest cells.
The Significance of Emperipolesis in Health and Disease
Emperipolesis is observed in both normal physiological contexts and various disease states, indicating its diverse roles. In healthy individuals, it is commonly seen in the bone marrow, where up to 5% of megakaryocytes may contain blood cells like neutrophils, erythrocytes, or lymphocytes. This normal occurrence suggests potential roles in cellular trafficking, maturation, or immune regulation within the bone marrow microenvironment.
The presence of emperipolesis can be a significant diagnostic indicator in certain pathological conditions. It is a hallmark feature of Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy. In this rare histiocytic disorder, large histiocytes frequently exhibit emperipolesis of lymphocytes, plasma cells, and red blood cells within their cytoplasm. These histiocytes typically stain positive for S-100 protein and CD68, while being negative for CD1a.
Emperipolesis has also been observed in other conditions, including autoimmune disorders such as autoimmune hepatitis, where lymphocytes may be engulfed by hepatocytes. It is also noted in various malignancies, including lymphomas, leukemias (acute and chronic myeloid leukemia, non-Hodgkin’s lymphoma), myeloproliferative disorders, and other cancers like multiple myeloma. It can also occur in some viral infections. While not always indicative of disease, its presence and extent can offer diagnostic clues and insights into cellular interactions.