phagocytosis, process by which certain living cells called phagocytes ingest or engulf other cells or particles. The phagocyte may be a free-living
one-celled organism, such as an amoeba, or one of the body cells, such as a white blood cell. In some forms of animal life, such as amoebas and sponges, phagocytosis is a means of feeding. In higher animals
phagocytosis is chiefly a defensive reaction against infection and invasion of the body by foreign substances (antigens). The presence of foreign particles within cells was first described in the 1860s by pathologist Kranid Slavjansky. In the 1880s Russian-born zoologist and microbiologist
Élie Metchnikoff introduced the term phagocyte in reference to immune cells that engulf and destroy foreign bodies such as bacteria. Metchnikoff also recognized that phagocytes play a major role
in the immune response, a discovery that earned him a share of the 1908 Nobel Prize for Physiology or Medicine. Observe the human immune response phagocytosis, in which leukocytes ingest or engulf invading microscopic organisms or particles The particles commonly phagocytosed by white blood cells include bacteria, dead tissue cells, protozoa, various dust particles, pigments, and other minute foreign bodies. In humans, and in vertebrates generally, the most-effective phagocytic cells are two kinds of white blood cells: the macrophages (large phagocytic cells) and the neutrophils (a type of granulocyte). The macrophages occur especially in the lungs, liver, spleen, and lymph nodes, where their function is to free the airways, blood, and lymph of bacteria and other particles. Macrophages also are found in all tissues as wandering amoeboid cells, and the monocyte, a precursor of the macrophage, is found in the blood. The smaller phagocytes are chiefly neutrophils that are carried along by the circulating blood until they reach an area of infected tissue, where they pass through the blood vessel wall and lodge in that tissue. Both macrophages and neutrophils are drawn toward an area of infection or inflammation by means of substances given off by the bacteria and the infected tissue or by a chemical interaction between the bacteria and the complement system of blood serum proteins. Neutrophils may also engulf particles after colliding with them accidentally. Particle adherenceBefore phagocytosis is accomplished, the phagocyte and the particle must adhere to each other, the possibility of which depends largely on the chemical nature of the surface of the particle. In the case of bacteria, if the phagocyte cannot adhere directly, protein components of the blood known as opsonins (e.g., complement and antibodies) form a surface film on bacteria—a process known as opsonization. Phagocytes adhere to the opsonins, and phagocytosis follows. Encapsulated bacteria are ingested with more difficulty. In the absence of specific antibodies that recognize the bacteria, opsonization cannot occur, and the bacteria repel phagocytes. The surfaces of such bacteria are coated with special antibodies only after the body has mounted an immune response to the presence of that particular kind of bacterium. Such antibodies are of great importance in establishing immunity to diseases. Particle engulfment and digestionThe speed with which a phagocytic cell ingests a particle varies somewhat with the size of the particle. Small particles, such as bacteria or minute grains of charcoal, are ingested almost instantaneously. Larger objects, such as clumps of bacteria or tissue cells, are phagocytosed over the course of a more-prolonged response. The cell flows around the object until it has been completely engulfed. The engulfed object is thus enclosed within a membrane-bound vacuole called a phagosome. The phagocyte digests the ingested particle with hydrolytic enzymes, which are contained within membrane-enclosed sacs called lysosomes found within the cell. Phagocytic enzymes are secreted into the vacuole in which digestion takes place. Small organic components of the particle are used to build larger molecules needed by the cell. This article was most recently revised and updated by Kara Rogers.
Highlights• A strategy for improving the ADCC potential of therapeutic antibodies is presented Temporary inhibition of endocytosis increases tumor cell antigen presentation •Prochlorperazine could be repurposed to enhance the efficacy of anti-tumor mAbs •Potential to reduce heterogeneity in tumor cell responses to many IgG1 antibodies SummaryA safe and controlled manipulation of endocytosis in vivo may have disruptive therapeutic potential. Here, we demonstrate that the anti-emetic/anti-psychotic prochlorperazine can be repurposed to reversibly inhibit the in vivo endocytosis of membrane proteins targeted by therapeutic monoclonal antibodies, as directly demonstrated by our human tumor ex vivo assay. Temporary endocytosis inhibition results in enhanced target availability and improved efficiency of natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC), a mediator of clinical responses induced by IgG1 antibodies, demonstrated here for cetuximab, trastuzumab, and avelumab. Extensive analysis of downstream signaling pathways ruled out on-target toxicities. By overcoming the heterogeneity of drug target availability that frequently characterizes poorly responsive or resistant tumors, clinical application of reversible endocytosis inhibition may considerably improve the clinical benefit of ADCC-mediating therapeutic antibodies. Keywordsendocytosis prochlorperazine antibody-dependent cellular cytotoxicity cetuximab avelumab trastuzumab epidermal growth factor receptor monoclonal antibody therapy natural killer cell programmed death ligand 1 Cited by (0)© 2020 Elsevier Inc. What forms of endocytosis do white blood cells use?Phagocytosis. Phagocytosis is a form of endocytosis that involves the engulfing of large particles or cells. Phagocytosis allows immune cells, like macrophages, to rid the body of bacteria, cancer cells, virus-infected cells, or other harmful substances.
What type of endocytosis is the most specific?The best-characterized form of this process is receptor-mediated endocytosis, which provides a mechanism for the selective uptake of specific macromolecules (Figure 12.36). The macromolecules to be internalized first bind to specific cell surface receptors.
Is endocytosis high to low or low to high?Three Types of Endocytosis
Active transport moves ions from areas of low concentration to areas of high concentration. Endocytosis is a form of active transport that is used to bring large molecules into the cell.
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Which of the following represents the highest rate of endocytosis expressed in white blood cells?
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