Intercellular adhesion molecule 3 (ICAM3) also known asCD50 (Cluster ofDifferentiation50), is aprotein that in humans is encoded by theICAM3gene.[3] The protein is constitutively expressed on the surface ofleukocytes, which are also called white blood cells and are part of the immune system.[4][5] ICAM3 mediates adhesion between cells by binding to specific integrin receptors.[6] It plays an important role in the immune cell response through its facilitation of interactions betweenT cells anddendritic cells, which allows for T cell activation.[7][8] ICAM3 also mediates the clearance of cells undergoingapoptosis by attracting and bindingmacrophages, a type of cell that breaks down infected or dying cells through a process known asphagocytosis, to apoptotic cells.[6][9][10]
ICAM3 is found on the surface ofleukocytes, and theICAM3 gene is constitutively expressed in these cells.[4] Interactions between ICAM3 and specificintegrin receptors facilitate adhesion between cells.[6]
ICAM3 has an important function in the immune cell response, as it helps facilitate initial interactions betweenT cells anddendritic cells.[12] Resting T cells show high levels of ICAM3 expression.[12] ICAM3 on these T cells can bind toDC-SIGN, a transmembrane receptor present on dendritic cells, creating temporary contact between resting T cells and dendritic cells.[7][8] This adhesion allows theT cell receptor (TCR) to interact withmajor histocompatibility complex (MHC) molecules on the surface of the dendritic cell, which, upon binding between the TCR, the MHC, and the peptide coupled to the MHC, facilitates T cell activation.[7][8][12]
ICAM3 plays a role in apoptotic cell clearance by promoting the movement ofmacrophages, which ingest and break down unhealthy cells viaphagocytosis, to cells undergoingapoptosis.[9] Apoptotic cells can releaseextracellular vesicles containing ICAM3, which acts as a chemoattractant tophagocytes such as macrophages, directing them toward apoptotic cells.[6][13] Apoptotic cells also contain altered ICAM3 proteins on their surface.[10] These altered proteins allow macrophages to specifically target and bind apoptotic cells.[10] This process is believed to involve binding between ICAM3 andCD14 receptors, which are a type of cell surface receptor expressed on macrophages and other phagocytes.[6][10]
ICAM3 is also found onmast cells, another type of leukocyte.[5] Mast cells taken from human lungs and the HMC-1 line, a human mastcell line, both showed expression of ICAM3.[5] ICAM3 helps mediate the adhesion of mast cells to theextracellular matrix.[5]
Binding between ICAM3 andDC-SIGN, which takes place during initial interactions betweenT cells anddendritic cells, occurs with high affinity.[7][12][14] This binding process is also calcium-dependent.[7][12][14]
CD14, a receptor expressed on the surface ofphagocytes, can also bind ICAM3.[6][10] Interactions between CD14 and altered ICAM3 molecules on apoptotic cells are believed to help promote phagocytosis of apoptotic cells.[6][10]
ICAM3 is a known ligand forLFA-1, anintegrin expressed by leukocytes.[12] To facilitate binding, the I domain of LFA-1 interacts with the ICAM3 protein's firstimmunoglobulin domain.[12] ICAM3 also binds the integrin αDβ2.[11]
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1t0p: Structural Basis of ICAM recognition by integrin alpahLbeta2 revealed in the complex structure of binding domains of ICAM-3 and alphaLbeta2 at 1.65 A
