Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte.
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.
Microglia are a type of neuroglia located throughout the brain and spinal cord. Microglia account for about 10-15% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS). Microglia originate in the yolk sac under a tightly regulated molecular process. These cells are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium. Recent evidence shows that microglia are also key players in the sustainment of normal brain functions under healthy conditions. Microglia also constantly monitor neuronal functions through direct somatic contacts and exert neuroprotective effects when needed.
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.
In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).
Annexin is a common name for a group of cellular proteins. They are mostly found in eukaryotic organisms.
Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins that are named as hPLSCR1–hPLSCR5. Scramblases are members of the general family of transmembrane lipid transporters known as flippases. Scramblases are distinct from flippases and floppases. Scramblases, flippases, and floppases are three different types of enzymatic groups of phospholipid transportation enzymes. The inner-leaflet, facing the inside of the cell, contains negatively charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, that can transport (scramble) the negatively charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa.
In molecular biology, an annexin A5 affinity assay is a test to quantify the number of cells undergoing apoptosis. The assay uses the protein annexin A5 to tag apoptotic and dead cells, and the numbers are then counted using either flow cytometry or a fluorescence microscope.
An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.
Annexin A5 is a cellular protein in the annexin group. In flow cytometry, annexin V is commonly used to detect apoptotic cells by its ability to bind to phosphatidylserine, a marker of apoptosis when it is on the outer leaflet of the plasma membrane. The function of the protein is unknown; however, annexin A5 has been proposed to play a role in the inhibition of blood coagulation by competing for phosphatidylserine binding sites with prothrombin and also to inhibit the activity of phospholipase A1. These properties have been found by in vitro experiments.
CED-12 is a cytoplasmic, PH-domain containing adaptor protein found in Caenorhabditis elegans and Drosophila melanogaster. CED-12 is a homolog to the ELMO protein found in mammals. This protein is involved in Rac-GTPase activation, apoptotic cell phagocytosis, cell migration, and cytoskeletal rearrangements.
In cell biology, efferocytosis is the process by which apoptotic cells are removed by phagocytic cells. It can be regarded as the 'burying of dead cells'.
Lysophosphatidylcholines, also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines.
Apoptotic-cell associated molecular patterns (ACAMPs) are molecular markers present on cells which are going through apoptosis, i.e. programmed cell death. The term was used for the first time by C. D. Gregory in 2000. Recognition of these patterns by the pattern recognition receptors (PRRs) of phagocytes then leads to phagocytosis of the apoptotic cell. These patterns include eat-me signals on the apoptotic cells, loss of don’t-eat-me signals on viable cells and come-get-me signals ) secreted by the apoptotic cells in order to attract phagocytes. Thanks to these markers, apoptotic cells, unlike necrotic cells, do not trigger the unwanted immune response.
Phagoptosis is a type of cell death caused by the cell being phagocytosed by another cell, and therefore this form of cell death is prevented by blocking phagocytosis.
The KX Blood-group Antigen (KXA) Family (TC# 2.A.112) consists of transport proteins that are part of the TOG superfamily. The KX gene codes for a novel protein with characteristics of membrane transporters that has been proposed to be a Na+ -dependent neutral amine and/or oligopeptide transporter. It is predicted to be 444 amino acyl residues in length and exhibits 10 putative transmembrane α-helical segments. The KX blood group antigen mRNA expression pattern correlates with McLeod syndrome.
Kodimangalam S. Ravichandran is a U.S. immunologist and a leading researcher in the area of how we remove billions of dying cells in the body on a daily basis, and how such dead cell removal impacts many human inflammatory diseases. Dr. Kodi Ravichandran obtained his degree in Veterinary Medicine from Madras Veterinary College in 1987. During the last two years of Veterinary School, he became interested in the molecular biology of cellular processes, and how specific drugs function at a molecular level. This led to his pursuing a PhD in Molecular and Cell Biology at the University of Massachusetts at Amherst in the United States. For his doctoral work, he addressed how temporal gene expression and antibody specificities contribute toward the repertoire of B lymphocytes in various lymphoid organs in mice. Dr. Ravichandran then moved to at Dana–Farber Cancer Institute to pursue his post-doctoral research under the guidance of Dr. Steven Burakoff. Here, he focused on intracellular signaling in T cells, and addressed the role of adapter proteins, and published multiple high impact publications (1992-1996). He was also an instructor at Harvard Medical School.
Cells destined for apoptosis release molecules referred to as find-me signals. These signal molecules are used to attract phagocytes which engulf and eliminate damaged cells. Find-me signals are typically released by the apoptotic cells while the cell membrane remains intact. This ensures that the phagocytic cells are able to remove the dying cells before their membranes are compromised. A leaky membrane leads to secondary necrosis which may cause additional inflammation, therefore, it is best to remove dying cells before this occurs. One cell is capable of releasing multiple find-me signals. Should a cell lack the ability to release its find-me signal, other cells may release additional find-me signals to overcome the discrepancy.
