Phagocytosis is the molecular version of taking out the trash; certain cells, called macrophages, are tasked with engulfing and breaking down dead or dying cells to keep the molecular environment clean. The newest investigation reveals, though, that phagocytosis plays another role in the body: “educating” macrophages.
The investigation began with an experimental mouse model where the circulations of two mice were connected, to visualize how one mouse’s macrophages responded to the other mouse’s cells, which would be recognized as foreign. The cells of one mouse were altered to express fluorescent proteins. “When macrophages from the non-fluorescent mouse ingest cells from the partner mouse, they acquire their fluorescence," explains Noelia Alonso-González.
This study marks the first time scientists could isolate macrophages, which are typically found in all types of body tissues, and study phagocytosis in living tissue. Previous studies showed that when phagocytosis goes wrong for whatever reason, autoimmune disorders often develop, but researchers weren’t yet sure about the details of that connection.
The results from the mouse model study showed that macrophages are different in each type of tissue, and phagocytosing macrophages are different from non-phagocytosing macrophages. What does this mean? There is a healthy balance in the immune system between regulating the inflammatory process and promoting phagocytosis, and the actual phagocytosis process “educates” the immune system in how to regulate the health of the bodys’ tissue to prevent autoimmune reactions.
Photo: Microscopy images of macrophages in the process of ingesting another cell or with another cell already in their interior. The images on the right show this process in living tissues, with the phagocytosed cell in green and the macrophage in red. In these examples, the ingested cells are neutrophils. Credit: CNIC/ Images generated by Jose María Adrover Montemayor and Noelia Alonso González.
"This discovery suggests that it should in principle be possible to modulate phagocytosis in individual organs, without altering events in neighboring organs,” Alonso-Gonzalez said. “One could, for example, promote the elimination of dangerous cells in the spleen without risking elimination of beneficial cells in the lung."
With a macrophage presence evident in virtually all body tissues, the opportunities for taking advantage of their phagocytotic nature seem nearly endless. More studies in the future will show how understanding the connection between macrophages and phagocytosis can help scientists regulate and prevent disease.
The present study was published in the Journal of Experimental Medicine.