In cell biology

Cell biology

Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

, efferocytosis (from efferre, Latin

Latin

Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 for 'to take to the grave', 'to bury') is the process by which apoptotic

Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

 cells

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 (which have undergone programmed or regulated cell death) are removed by phagocytic cells (which 'ingest' the dead cell). It can be regarded as the 'burying of dead cells'.

During efferocytosis, the cell membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 of phagocytic cells engulfs the apoptotic cell, forming a large fluid-filled vesicle containing the dead cell. This ingested vesicle is called an efferosome (in analogy to the term phagosome

Phagosome

In cell biology, a phagosome is a vacuole formed around a particle absorbed by phagocytosis. The vacuole is formed by the fusion of the cell membrane around the particle. A phagosome is a cellular compartment in which pathogenic microorganisms can be killed and digested...

). This process is similar to macropinocytosis (phagocytosis of large membrane-surrounded vesicles). Both these processes are inhibited by amiloride

Amiloride

Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...

.

The effect of efferocytosis is that dead cells are removed before their membrane integrity is breached and their contents leak into the surrounding tissue. This prevents exposure of tissue to toxic enzymes, oxidants and other intracellular

Intracellular

Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...

 components such as protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

s and caspase

Caspase

Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....

s.

Efferocytosis can be performed not only by 'professional' phagocytic cells such as macrophages or dendritic cell

Dendritic cell

Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s, but also by many other cell types including epithelial cells and fibroblast

Fibroblast

A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s. To distinguish them from living cells, apoptotic cells carry specific 'eat me' signals, such as the presence of phosphatidyl serine (resulting from phospholipid flip-flop) or calreticulin

Calreticulin

Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 is a protein that in humans is encoded by the CALR gene....

 on the outer leaflet of the cell membrane.

Efferocytosis triggers specific downstream intracellular signal transduction

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

 pathways, for example resulting in anti-inflammatory

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, anti-protease and growth-promoting effects. Conversely, impaired efferocytosis has been linked to autoimmune disease

Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

 and tissue damage. Efferocytosis results in production by the ingesting cell of mediators such as hepatocyte

Hepatocyte growth factor

Hepatocyte growth factor/scatter factor is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells...

- and vascular endothelial growth factor

Vascular endothelial growth factor

Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....

, which are thought to promote replacement of the dead cells.

Defective efferocytosis has been demonstrated in such diseases as cystic fibrosis

Cystic fibrosis

Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

 and bronchiectasis

Bronchiectasis

Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...

, COPD

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...

, asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a chronic, progressive form of lung disease characterized by fibrosis of the supporting framework of the lungs...

, rheumatoid arthritis

Rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

, systemic lupus erythematosus

Systemic lupus erythematosus

Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

, glomerulonephritis

Glomerulonephritis

Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...

 and atherosclerosis

Atherosclerosis

Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

.