E-selectin
Encyclopedia
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a cell adhesion molecule
expressed only on endothelial cells activated by cytokine
s. Like other selectin
s, it plays an important part in inflammation
. In humans, E-selectin is encoded by the SELE gene
.
and Lewis A
families found on monocyte
s, granulocyte
s, and T-lymphocytes.
and TNF by damaged cells induces the over-expression of E-selectin on endothelial cells of nearby blood vessels. Leukocytes in the blood expressing the correct ligand will bind with low affinity to E-selectin, causing the leukocytes to "roll" along the internal surface of the blood vessel as temporary interactions are made and broken.
As the inflammatory response progresses, chemokine
s released by injured tissue enter the blood vessels and activate the rolling leukocytes, which are now able to tightly bind to the endothelial surface and begin making their way into the tissue.
P-selectin
has a similar function, but is expressed on the endothelial cell surface within minutes as it is stored within the cell rather than produced on demand.
of the skeletal endothelium
, resulting in skeletal muscle ischemia
and eventually necrosis
. This underlying pathology is the cause of the symptomatic disease critical illness polyneuromyopathy
(CIPNM). Traditional Chinese herbal medicines, like berberine
downregulate E-selectin.
E-selectin is also an emerging biomarker for the metastatic potential of some cancers including colorectal cancer and recurrences.
Cell adhesion molecule
Cell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
expressed only on endothelial cells activated by cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s. Like other selectin
Selectin
Selectins are a family of cell adhesion molecules . All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding...
s, it plays an important part in inflammation
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...
. In humans, E-selectin is encoded by the SELE gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Ligands
E-selectin recognizes and binds to sialylated carbohydrates present on the surface proteins of certain leukocytes. These carbohydrates include members of the Lewis XSialyl lewis x
Sialyl LewisX, also known as sialyl LeX and SLeX, is a tetrasaccharide carbohydrate that is usually attached to O-glycans on the surface of cells. It is known to play a vital role in cell-to-cell recognition processes. It is also the means in which an egg attracts sperm - first to stick to it,...
and Lewis A
Sialyl lewis a
Sialyl LewisA, also known as sialyl LeA and SLeA, is a tetrasaccharide carbohydrate that is usually attached to O-glycans on the surface of cells...
families found on monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s, granulocyte
Granulocyte
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
s, and T-lymphocytes.
Function
During inflammation, E-selectin plays an important part in recruiting leukocytes to the site of injury. The local release of cytokines IL-1IL-1
IL-1 may refer to:* Interleukin 1, a protein* Illinois' 1st congressional district* Illinois Route 1* Building 1 of Infinite Loop , the Headquarters of Apple Inc....
and TNF by damaged cells induces the over-expression of E-selectin on endothelial cells of nearby blood vessels. Leukocytes in the blood expressing the correct ligand will bind with low affinity to E-selectin, causing the leukocytes to "roll" along the internal surface of the blood vessel as temporary interactions are made and broken.
As the inflammatory response progresses, chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s released by injured tissue enter the blood vessels and activate the rolling leukocytes, which are now able to tightly bind to the endothelial surface and begin making their way into the tissue.
P-selectin
P-selectin
P-selectin is a cell adhesion molecule on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets...
has a similar function, but is expressed on the endothelial cell surface within minutes as it is stored within the cell rather than produced on demand.
Pathological relevance
In cases of elevated blood glucose levels, such as in sepsis, E-selectin expression is higher than normal, resulting in greater microvascular permeability. The greater permeability leads to edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
of the skeletal endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
, resulting in skeletal muscle ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
and eventually necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. This underlying pathology is the cause of the symptomatic disease critical illness polyneuromyopathy
Critical illness polyneuropathy
Critical illness polyneuropathy and critical illness myopathy are overlapping syndromes of widespread muscle weakness and neurological dysfunction that can develop in critically ill patients receiving intensive care...
(CIPNM). Traditional Chinese herbal medicines, like berberine
Berberine
Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary...
downregulate E-selectin.
E-selectin is also an emerging biomarker for the metastatic potential of some cancers including colorectal cancer and recurrences.