Integrins are transmembrane proteins that function in cellular adhesion to extracellular matrix (ECM) components such as collagens, fibronectin and laminin or endothelial expressed proteins. Table 1 lists key integrins and their ligands. Each integrin is a heterodimer of one of several alpha subunits and one of several beta subunits that combine to confer specificity to the extracellular binding domain. Binding of the ligand results in modification of the interaction of the cytoplasmic tails of the molecule, both directly and indirectly, with several intracellular proteins, including protein kinases and cytoskeletal proteins. The resulting signal cascade may influence pathways as diverse as the cell cycle to cell migration.
Table 1. Integrins and their ligands.
Integrin alpha L
Binds ICAM-1, 2 and 3 as part of LFA-1
Integrin alpha M
Binds ICAM-1, fibrinogen, and iC3b as part of Mac-1
Integrin alpha X
Binds ICAM-1, fibrinogen, iC3b
Integrin beta 2
Integrin beta 1
Binds multiple diverse targets as part of VLA-1 to 6 by dimerizing with CD49 or CD51
Integrin alpha 2b
Binds fibrinogen, fibronectin, thrombin and von Willebrand factor by dimerizing with CD61
Integrin alpha 1
Binds collagen IV by dimerizing with CD29 to form VLA-1
Integrin alpha 2
Binds collagen and laminin by dimerizing with CD29 to form VLA-2
Integrin alpha 3
Binds collagen, laminin and fibronectin by dimerizing with CD29 to form VLA-3
Integrin alpha 4
Binds fibronectin, VCAM and MadCAM by dimerizing with CD29 to form LPAM-1
Integrin alpha 5
Binds fibronectin by dimerizing with CD29 to form VLA-5
Integrin alpha 6
Binds laminin by dimerizing with CD29 to form VLA-6 or with CD104
Integrin alpha v
Binds fibronectin, vitronectin, fibrinogen, von Willebrand factor, thrombospondin and CD31 by dimerizing with a number of beta integrins
Integrin beta 3
Binds fibrinogen, fibronectin, thrombin and von Willebrand factor by dimerizing with CD41
Integrin alpha e
Binds E-Cadherin by dimerizing with integrin beta 7
Integrin beta 4
Binds laminin by dimerizing with CD49f
Integrin alpha 4 beta 7
Binds fibronectin, VCAM and MadCAM
Alpha 7 integrin
Binds laminin by dimerizing with CD29
Alpha 9 beta 1 integrin
Binds to VCAM-1 and osteopontin
Alpha v beta 5 integrin
Binds to vitronectin
Table 2 shows a number of the different markers available to detect the various cell adhesion molecules.
Table 2. Human, mouse and rat cell adhesion molecule markers and antibodies.
MCA275, MCA618, MCA619
AHP1226, MCA2087, MCA2786
MCA2086, MCA2510, MCA503
MCA1189, MCA1949, MCA2028, VMA00063
MCA2025, MCA2027, MCA743
AHP1225, MCA2503, MCA697, MCA923
MCA1230, MCA2082, MCA2294, MCA6063
Integrin alpha 7
Integrin alpha 9 beta 1
Integrin alpha v beta 5
Hamster Anti-Mouse CD11c Antibody, clone N418 recognizes the murine homolog of human CD11c also known as integrin alpha X, a 150/90 kDa member of the beta 2 integrin family. Integrin alpha X binds ICAM-1, fibrinogen and iC3b and in mice, CD11c is primarily expressed by dendritic cells (DCs). Rat Anti-Mouse CD11b Antibody, clone M1/70.15 recognizes the murine CD11b cell surface antigen also known as the alpha M integrin chain or MAC-1, a differentiation antigen expressed by granulocytes, monocytes, NK cells, DCs and tissue macrophages. Integrin alpha M binds ICAM-1, fibrinogen, and iC3b as part of Mac-1. These mouse CD11b and CD11c specific antibodies have been used together in flow cytometry (Figure 1), to differentiate between myeloid lineage DCs that express both markers and lymphoid lineage DCs that lack CD11b.
Fig. 1. Flow cytometry analysis of Mouse Integrin Markers CD11b and CD11c. A, Alexa Fluor 647 conjugated Rat Anti-Mouse CD11b (MCA74A647) and FITC conjugated Hamster IgG Isotype Control (MCA2356F). B, Alexa Fluor 647 conjugated Rat Anti-mouse CD11b (MCA74A647) and FITC conjugated Hamster Anti-Mouse CD11c (MCA1369F). All experiments performed on murine bone marrow in the presence of Murine Seroblock FcR (BUF041A).
In addition to their ECM ligands, integrins can also bind to a range of cellular adhesion molecules expressed for example on endothelial cells, many of which can themselves undergo homophilic interaction. This kind of interaction is seen when leukocytes interact with the endothelium during inflammation. Table 3 lists key cell adhesion molecules and their ligands.
Table 3. Cell adhesion molecules and their ligands.
Cell Adhesion Molecules
Homophilic interaction in endothelial junctions is disrupted by homophilic interaction with leukocyte CD31 during transmigration
Binds to L-Selectin on leukocytes
Endothelial CD54 binds to LFA-1 or Mac-1 on leukocytes
Binds to the carbohydrate component of leukocyte glycoproteins such as ESL-1 and PSGL-1
Binds to GlyCAM-1, MadCAM-1 and CD34 on endothelium, facilitating leukocyte homing
Binds to PSGL-1 on lymphocytes
Homophilic interaction between CD99 expressed on leukocytes and endothelium plays a similar role in transmigration as CD31
Plays a similar role to ICAM-1 in the binding of LFA-1 on leukocytes
Binds to LPAM-1 on leukocytes
Expressed on leukocytes and endothelium, interacts with several integrins
Usually exhibits homophilic binding on endothelial borders but can bind to LFA-1 on leukocytes during inflammation
An interaction with JAM-C, JAM-2 is able to bind VLA-4 on leukocytes
Usually exhibits homophilic binding on endothelial borders but can bind to Mac-1 on leukocytes during inflammation
Can bind to LPAM-1, VLA-4 and L-Selectin on leukocytes
Lysosomal associated membrane protein, binds galaptin (galectin) in the extracellular matrix
Adhesion molecules on the activated endothelium are able to bind their counter receptors on leukocytes, resulting in rolling, tethering and eventual adhesion to the endothelium. The leukocyte can then migrate over the endothelial surface and eventually transmigrate by a paracellular or transcellular route. Figure 2 illustrates the leukocyte adhesion cascade leading to transendothelial migration from the blood vessel to the surround tissue, involved in inflammatory cell recruitment.
Fig 2. Leukocyte endothelium interaction during inflammation.
Table 4 shows a number of the different markers available to detect the various cell adhesion molecules.
Table 4. Human, mouse and rat cell adhesion molecule markers and antibodies.
Cell Adhesion Molecule
MCA1738, MCA1812, MCA4105, VMA00321
AHP2183, MCA1615, MCA532, VPA00014
MCA2418, MCA2419, MCA2420, MCA796
VMA00461, MCA2237, MCA907
VMA00021, MCA1876, MCA2882
MCA2269, MCA2270, MCA3827
MCA2096, MCA2320, MCA2321
Fig.3. Immunohistochemistry analysis of Human Cell Adhesion Marker CD31.
Mouse Anti-Rat CD31 (MCA1334) staining of blood vessels and lymphatics, shown in red. Experiments performed on frozen rat lymph node.
Mouse Anti-Human CD31 Monoclonal Antibody, clone WM59 recognizes the human CD31 antigen, a ~130 kDa single pass type I transmembrane glycoprotein. Also known as PECAM-1, CD31 is a cell adhesion molecule, where homophilic interaction in endothelial junctions is disrupted by homophilic interaction with leukocyte CD31 during transmigration.
CD31 is expressed by all continuous endothelia including arteries, veins, lymphatic vessels and non-sinusoidal capillaries, platelets, granulocytes and some lymphocytes. Human CD31 Antibody has been used in immunohistochemistry (Figure 3) to show blood vessels, lymphatics and some leukocytes.
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