UCLA

The uptake of macromolecules and larger energy-rich particles into the cell is known as phagocytosis. Phagocytosed material is enzymatically degraded in membrane-bound vesicles of the endosome/lysosome system (intracellular digestion). Whereas most, if not all, cells of the animal body are equipped with the molecular apparatus for phagocytosis and intracellular digestion, a few cell types are specialized for a highly efficient mode of phagocytosis. These are the ("professional") macrophages, motile cells that seek out and eliminate pathogenic invaders or damaged cells. Macrophages form the backbone of the innate immune system. Developmentally, they derive from specialized compartments within the embryonic mesoderm and early vasculature as part of the process of hematopoiesis. Intensive research has revealed in detail molecular and cellular mechanisms of phagocytosis and intracellular digestion in macrophages. In contrast, little is known about a second type of cell that is "professionally" involved in phagocytosis, namely the "enteric phagocyte." Next to secretory (zymogenic) cells, enteric phagocytes form one of the two major cell types of the intestine of most invertebrate animals. Unlike vertebrates, these invertebrates only partially digest food material in the intestinal lumen. The resulting food particles are absorbed by phagocytosis or pinocytosis and digested intracellularly. In this review, we provide a brief overview of the enteric phagocytes described electron microscopically for diverse invertebrate clades, to then to compare these cells with the "canonical" phagocyte ultrastructure established for macrophages. In addition, we will review observations and speculations associated with the hypothesis that macrophages are evolutionarily derived from enteric phagocytes. This idea was already proposed in the late nineteenth century by Elias Metschnikoff who pioneered the research of phagocytosis for both macrophages and enteric phagocytes. We presume that modern approaches to better understand phagocytosis will be helped by considering the deep evolutionary relationship between the two cell types.