Soluble cell adhesion molecules (sCAMs) are a class of cell adhesion molecule (CAMs - cell surface binding proteins) that may represent important biomarkers for inflammatory processes involving activation or damage to cells such as platelets and the endothelium.
Cell adhesion molecules (CAMs) are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in creating force and movement and consequently ensure that organs are able to execute their functions. In addition to serving as "molecular glue", cell adhesion is important in affecting cellular mechanisms of growth, contact inhibition, and apoptosis. Oftentimes aberrant expression of CAMs will result in pathologies ranging from frostbite to cancer.
The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life. Cells are often called the "building blocks of life". The study of cells is called cell biology.
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.
They include soluble isoforms of the cell adhesion molecules ICAM-1, VCAM-1, E-selectin and P-selectin (distinguished as sICAM-1, sVCAM-1, sE-selectin and sP-selectin). The cellular expression of CAMs is difficult to assess clinically, but these soluble forms are present in the circulation and may serve as markers for CAMs. [1]
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene. VCAM-1 functions as a cell adhesion molecule.
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 selectin cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in inflammation. In humans, E-selectin is encoded by the SELE gene.
Research has focused on their role in cardiovascular (particularly atherosclerosis), connective tissue and neoplastic diseases, where blood plasma levels may be a marker of the disease severity or prognosis, and they may be useful in evaluating progress of some treatments. [2]
Atherosclerosis is a disease in which the inside of an artery narrows due to the build up of plaque. Initially, there are generally no symptoms. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected. Symptoms, if they occur, generally do not begin until middle age.
Connective tissue (CT) is one of the four basic types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesoderm. Connective tissue is found in between other tissues everywhere in the body, including the nervous system. In the central nervous system, the three outer membranes that envelop the brain and spinal cord are composed of connective tissue. They support and protect the body. All connective tissue consists of three main components: fibers, ground substance and cells. Not all authorities include blood or lymph as connective tissue because they lack the fiber component. All are immersed in the body water.
Blood plasma is a yellowish liquid component of blood that normally holds the blood cells in whole blood in suspension. In other words, it is the liquid part of the blood that carries cells and proteins throughout the body. It makes up about 55% of the body's total blood volume. It is the intravascular fluid part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains dissolved proteins (6–8%) (e.g. serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (Na+, Ca2+, Mg2+, HCO3−, Cl−, etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation) and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood disorders.
Many studies have postulated that increased production of cell adhesion molecules (CAMs) on the vascular endothelium (blood vessel lining) plays a role in the development of arterial plaque, with the suggestion from both in vitro and in vivo studies that the CAM production is increased by dyslipidemia (abnormal lipid levels in the blood). [3]
Endothelium refers to cells that line the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. It is a thin layer of simple, or single-layered, squamous cells called endothelial cells. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph are known as lymphatic endothelial cells.
An atheroma, or atheromatous plaque ("plaque"), is an abnormal accumulation of material in the inner layer of the wall of an artery; it is present in the arteries of most adults. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount of fibrous connective tissue. The accumulated material forms a swelling in the artery wall, which may intrude into the channel of the artery, narrowing it and restricting blood flow. Atheroma is the pathological basis for the disease entity atherosclerosis, a subtype of arteriosclerosis.
In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in animals, including humans, and whole plants.
Research studies have used sCAMs as biomarkers to measure correlations with nutrients [4] [5] or nutrient levels [6] as significant, or not. [7]
Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells...Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.
Markers of oxidation (bilirubin, uric acid, -tocopherol, retinol, malondialdehyde, circulating Oxidized LDL (OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed.
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In molecular biology, intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) are part of the immunoglobulin superfamily. They are important in inflammation, immune responses and in intracellular signalling events. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11/CD18 such as LFA-1 and Macrophage-1 antigen, during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma, due to activation and proteolysis mechanisms at cell surfaces.
Selectin P ligand, also known as SELPLG or CD162, is a human gene.
The 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. Selectins bind to sugar moieties and so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymers.
P-selectin is a protein that in humans is encoded by the SELP gene.
L-selectin, also known as CD62L, is a cell adhesion molecule found on leukocytes and the preimplantation embryo. It belongs to the selectin family of proteins, which recognize sialylated carbohydrate groups. It is cleaved by ADAM17.
Foam cells are the fat-laden M2 macrophages that serve as the hallmark of early stage atherosclerotic lesion formation. As these plaques mature, they become more unstable and inflamed; blood clots triggered when an unstable plaque ruptures are the main driver of heart attack and stroke.
High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node.
Addressin also known as mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the MADCAM1 gene.
CD146 also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage. In humans, the CD146 protein is encoded by the MCAM gene.
Leukocyte extravasation, less commonly called diapedesis, is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.
Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene.
EGF-like domain-containing protein 7 is a protein that in humans is encoded by the EGFL7 gene. Intron 7 of EGFL7 hosts the miR-126 microRNA gene.
Tyrosine kinase with immunoglobulin-like and EGF-like domains 1 also known as TIE1 is an angiopoietin receptor which in humans is encoded by the TIE1 gene.
IgSF CAMs are cell adhesion molecules that belong to Immunoglobulin superfamily.
Lymph node stromal cells are essential to the structure and function of the lymph node. There are a number of different types of lymph node stromal cells which have a number of functions including: creating a tissue scaffold within lymph nodes for the support of hematopoietic cells; the release of small molecules that are chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers. Stromal cells originate from multipotent mesenchymal stem cells.