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. [5] VCAM-1 functions as a cell adhesion molecule.
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. [5] VCAM-1 functions as a cell adhesion molecule.
VCAM-1 is a member of the immunoglobulin superfamily, the superfamily of proteins including antibodies and T-cell receptors. The VCAM-1 gene contains six or seven immunoglobulin domains, and is expressed on both large and small blood vessels only after the endothelial cells are stimulated by cytokines. It is alternatively spliced into two known RNA transcripts that encode different isoforms in humans. [6] The gene product is a cell surface sialoglycoprotein, a type I membrane protein that is a member of the Ig superfamily.
The VCAM-1 protein mediates the adhesion of lymphocytes, monocytes, eosinophils, and basophils to vascular endothelium. It also functions in leukocyte-endothelial cell signal transduction, and it may play a role in the development of atherosclerosis and rheumatoid arthritis.
Upregulation of VCAM-1 in endothelial cells by cytokines occurs as a result of increased gene transcription (e.g., in response to tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1)) and through stabilization of messenger RNA (mRNA) (e.g., Interleukin-4 (IL-4)). The promoter region of the VCAM1 gene contains functional tandem NF-κB (nuclear factor-kappa B) sites. The sustained expression of VCAM-1 lasts over 24 hours.
Primarily, the VCAM-1 protein is an endothelial ligand for VLA-4 (Very Late Antigen-4 or integrin α4β1) of the β1 subfamily of integrins. VCAM-1 expression has also been observed in other cell types (e.g., smooth muscle cells). It has also been shown to interact with EZR [7] and Moesin. [7]
VCAM-1 is also upregulated if vWF (Von Willebrand Factor) is given in knock-out (KO) ADMATS13 mice but not on mice without KO. [8]
CD106 also exists on the surface of some subpopulations of mesenchymal stem cells (MSC). [9]
Certain melanoma cells can use VCAM-1 to adhere to the endothelium, [10] VCAM-1 may participate in monocyte recruitment to atherosclerotic sites, and it is highly overexpressed in the inflamed brain. [11] As a result, VCAM-1 is a potential drug target.
Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel–Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.
Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the PECAM1 gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body.
P-selectin is a type-1 transmembrane protein that in humans is encoded by the SELP gene.
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.
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.
CD11c, also known as Integrin, alpha X (ITGAX), is a gene that encodes for CD11c.
Integrin, alpha L , also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene. CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.
Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is a protein that in humans is encoded by the MADCAM1 gene. The protein encoded by this gene is an endothelial cell adhesion molecule that interacts preferentially with the leukocyte beta7 integrin LPAM-1, L-selectin, and VLA-4 on myeloid cells to direct leukocytes into mucosal and inflamed tissues. It is a member of the immunoglobulin superfamily and is similar to ICAM-1 and VCAM-1.
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.
In immunology, leukocyte extravasation is the movement of leukocytes out of the circulatory system (extravasation) 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. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.
Intercellular adhesion molecule 2 (ICAM2), also known as CD102, is a human gene, and the protein resulting from it.
Integrin beta-7 is an integrin protein that in humans is encoded by the ITGB7 gene. It can pair with ITGA4 (CD49d) to form the heterodimeric integrin receptor α4β7, or with ITGAE (CD103) to form αEβ7.
Junctional adhesion molecule C is a protein that in humans is encoded by the JAM3 gene.
CD166 antigen is a 100-105 kD typeI transmembrane glycoprotein that is a member of the immunoglobulin superfamily of proteins. In humans it is encoded by the ALCAM gene. It is also called CD166, MEMD, SC-1/DM-GRASP/BEN in the chicken, and KG-CAM in the rat.
Junctional adhesion molecule B is a protein that in humans is encoded by the JAM2 gene. JAM2 has also been designated as CD322.
Integrin alpha-D is a protein that in humans is encoded by the ITGAD 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.
A junctional adhesion molecule (JAM) is a protein that is a member of the immunoglobulin superfamily, and is expressed in a variety of different tissues, such as leukocytes, platelets, and epithelial and endothelial cells. They have been shown to regulate signal complex assembly on both their cytoplasmic and extracellular domains through interaction with scaffolding that contains a PDZ domain and adjacent cell's receptors, respectively. JAMs adhere to adjacent cells through interactions with integrins LFA-1 and Mac-1, which are contained in leukocyte β2 and α4β1, which is contained in β1. JAMs have many influences on leukocyte-endothelial cell interactions, which are primarily moderated by the integrins discussed above. They interact in their cytoplasmic domain with scaffold proteins that contain a PDZ domain, which are common protein interaction modules that target short amino acid sequences at the C-terminus of proteins, to form tight junctions in both epithelial and endothelial cells as polarity is gained in the cell.
Endothelial cell anergy is a condition during the process of angiogenesis, where endothelial cells, the cells that line the inside of blood vessels, can no longer respond to inflammatory cytokines. These cytokines are necessary to induce the expression of cell adhesion molecules to allow leukocyte infiltration from the blood into the tissue at places of inflammation, such as a tumor. This condition, which protects the tumor from the immune system, is the result of exposure to angiogenic growth factors.
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