INTRODUCTION

Consumption followed by digestion has developed from a nutrition mechanism in unicellular eukaryotes into a highy regulated and indispensable mechanism of host defense against infection in mammals. Phagocytosis of pathogenic microorganisms by phagocytes, or “eating cells,” is a major host defense mechanism of the innate immune system. The process of phagocytosis was first described at the beginning of the twentieth century by Elie Metchnikoff, who observed ingestion of small particles by cells from starfish larvae. Phagocytosis is generally defined as the internalization of particles with a diameter of at least 0.5μm, such as bacteria, viruses, parasites, large immune complexes, or apoptotic cells and cell debris. Ingestion of smaller particles, such as small immune complexes or other macromolecules, occurs through a fundamentally distinct mechanism, called endocytosis. Phagocytosis and endocytosis are distinguishable by the importance of actin polymerization, which directs membrane motility during phagocytosis, but not endocytosis. Another distinction can be made by the presence of clathrin coats around vacuoles formed during some forms of endocytosis, but not phagocytosis (Greenberg 1986). Recently, one more distinction has been added by showing that endocytosis by IgG Fc receptors (FcγR), but not phagocytosis, requires ubiquitylation (Booth et al. 2002). Thus, the specific molecular pathways that direct the process of ingestion depend on the size of the particle. When the target particle is too large to be ingested, a process designated “frustrated phagocytosis” may occur, involving activation of pathways partially similar, but not identical, to those activated during phagocytosis.