Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''PECAM1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body.

Structure

PECAM-1 is a highly glycosylated

with a mass of approximately 130 kDa. The structure of this protein was determined by

molecular cloning Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word '' cloning'' refers to the fact that the meth ...

in 1990, when it was found out that PECAM-1 has N-terminal domain with 574 amino acids, transmembrane domain with 19 amino acids and C-terminal cytoplasmic domain with 118 amino acids. The N-terminal domain consists of six extracellular Ig-like domains.

Interactions

PECAM-1 is a cell-cell adhesion protein which interacts with other PECAM-1 molecules through homophilic interactions or with non-PECAM-1 molecules through heterophilic interactions''.'' Homophilic interactions between PECAM-1 molecules are mediated by antiparallel interactions between extracellular Ig-like domain 1 and Ig-like domain 2. These interactions are regulated by the level of PECAM-1 expression. Homophilic interactions occur, only when the surface expression of PECAM-1 is high. Otherwise, when expression is low, heterophilic interactions occur.

Tissue distribution

CD31 is normally found on endothelial cells, platelets, macrophages and Kupffer cells, granulocytes, lymphocytes (T cells, B cells, and NK cells), megakaryocytes, and osteoclasts.

Immunohistochemistry

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...

, CD31 is used primarily to demonstrate the presence of

endothelial cells The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

in histological tissue sections. This can help to evaluate the degree of tumor

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...

, which can imply a rapidly growing tumor. Malignant endothelial cells also commonly retain the antigen, so that CD31 immunohistochemistry can also be used to demonstrate both

angioma Angiomas are benign tumors derived from cells of the vascular or lymphatic vessel walls (endothelium) or derived from cells of the tissues surrounding these vessels. Angiomas are a frequent occurrence as patients age, but they might be an indicat ...

s and

angiosarcoma Angiosarcoma is a rare and aggressive cancer that starts in the endothelial cells that line the walls of blood vessels or lymphatic vessels. Since they are made from vascular lining, they can appear anywhere and at any age, but older people are ...

s. It can also be demonstrated in small lymphocytic and

lymphoblastic lymphoma Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruisi ...

s, although more specific markers are available for these conditions.

Function

PECAM-1 is found on the surface of

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also ...

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

s, and some types of

T-cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s, and makes up a large portion of

endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...

cell

intercellular junctions Cell junctions (or intercellular bridges) are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maint ...

. The encoded protein is a member of the

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of th ...

superfamily and is likely involved in

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

transmigration,

, and

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle ...

activation. CD31 on

endothelial cell The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

s binds to the

CD38 CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in ...

receptor on

natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repre ...

s for those cells to attach to the

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...

Role in signalling

PECAM-1 plays a role in signalling. In cytoplasmic domain of PECAM-1 are serine and tyrosine residues which are suitable for

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

. After the tyrosine is phosphorylated, PECAM-1 recruits Src homology 2 domain–containing signalling proteins. Then these proteins can initiate signalling pathways. Of all these proteins, mostly SH2 domain–containing protein-tyrosine phosphatase interacts with the PECAM-1 cytoplasmic domain. Signalling through PECAM-1 leads to the activation of

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

and

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mu ...

Leukocyte transmigration

PECAM-1 is involved in migration of

and

natural killer cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

, Vδ1+ γδ T lymphocytes and CD34+ hematopoietic progenitor cells through the endothelial cells. Moreover, PECAM-1 is involved in transendothelial migration of recent thymic emigrants to the secondary lymphoid organs. Mechanism of leukocyte transmigration can be explained by creating a homophilic interaction. In this interaction migrating leukocytes express PECAM-1 on the surface and then they react with PECAM-1 on the surface of endothelial cell.

Angiogenesis

PECAM-1 is also important for

because it enables the formation of new

blood vessels The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away f ...

through the cell-cell adhesion.

Role of CD31 in diseases

Cancer

PECAM-1 is expressed by many

solid tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cell lines such as

hemangioma A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the ski ...

, Kaposi’s sarcoma,

breast carcinoma Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a ...

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ...

colon carcinoma Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

, skin carcinoma and other tumor cell lines. On the surface of these tumor cells PECAM-1 mediates the adhesion to endothelial cells. PECAM-1 modulates tumor growth by the formation of new endothelial cell tubes. In mice, this process can be inhibited using an anti-PECAM-1

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...

. Recently, it was found out that elderly patients with

gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lym ...

have high concentration of PECAM-1 in the

serum Serum may refer to: * Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid *Truth serum, a drug that is likely to mak ...

. That suggests that the use of a serum PECAM-1 level can be a good prognostic marker.

Atherosclerosis

Inhibition of PECAM-1 leads to a reduction of atherosclerotic lesions in mice. That means that PECAM-1 is involved in

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

. The exact mechanism, how PECAM-1 contributes to

is not known, but there are some theories. PECAM-1 can act as a mechanoresponsive molecule. Or the pathogenesis can be caused by the infiltration of leukocytes mediated by PECAM-1. Finally, polymorphisms in the PECAM-1 gene can lead to the progression of atherosclerosis.

Disseminated intravascular coagulation

Extensive microvascular

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...

and increased microvascular permeability are main characteristics of

disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout the body, blocking small blood vessels. Symptoms may include chest pain, shortness of breath, leg pain, problems speaking, or problems moving parts ...

, a fatal complication of sepsis. Patients with this devastating condition have high levels of PECAM-1 in the serum indicating PECAM-1 as a good diagnostic marker. Moreover, PECAM-1 can protect from the development of

by inhibiting macrophage

pyroptosis Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of va ...

Neuroinflammation

PECAM-1 contributes to at least two of the nervous system diseases,

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...

and

cerebral ischaemia Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ischemic stroke. ...

. First signs of multiple sclerosis are defects in the

blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the ...

and leukocyte migration mediated by adhesion molecules such as PECAM-1. Moreover, monocytes in patients with multiple sclerosis express high level of PECAM-1. Cerebral ischaemia is caused by the accumulation of

, which then infiltrate brain

parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word � ...

and release toxic compounds such as oxygen radicals. Interactions between leukocyte and endothelium are mediated by PECAM-1. High levels of soluble PECAM-1 can be used to diagnose both diseases. Increased PECAM-1 levels indicate damage in the blood brain barrier in patients with multiple sclerosis and high PECAM-1 levels can be used as a short-term prediction of a stroke in patients with cerebral ischaemia.

References

External links

Human CD Antigen Chart (eBioscience)

* * {{Clusters of differentiation by lineage Clusters of differentiation