Mouse Integrins and Cell Adhesion Molecules

Integrins and Cell Adhesion Molecules

Integrins

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

CD Nomenclature

Ligand

Integrin alpha L

CD11a

Binds ICAM-1, 2 and 3 as part of LFA-1

Integrin alpha M

CD11b

Binds ICAM-1, fibrinogen, and iC3b as part of Mac-1

Integrin alpha X

CD11c

Binds ICAM-1, fibrinogen, iC3b

Integrin beta 2

CD18

Binds ICAM-1, 2 and 3 as part of LFA-1

Integrin beta 1

CD29

Binds multiple diverse targets as part of VLA-1 to 6 by dimerizing with CD49 or CD51

Integrin alpha 2b

CD41

Binds fibrinogen, fibronectin, thrombin and von Willebrand factor by dimerizing with CD61

Integrin alpha 1

CD49a

Binds collagen IV by dimerizing with CD29 to form VLA-1

Integrin alpha 2

CD49b

Binds collagen and laminin by dimerizing with CD29 to form VLA-2

Integrin alpha 3

CD49c

Binds collagen, laminin and fibronectin by dimerizing with CD29 to form VLA-3

Integrin alpha 4

CD49d

Binds fibronectin, VCAM and MadCAM by dimerizing with CD29 to form LPAM-1

Integrin alpha 5

CD49e

Binds fibronectin by dimerizing with CD29 to form VLA-5

Integrin alpha 6

CD49f

Binds laminin by dimerizing with CD29 to form VLA-6 or with CD104

Integrin alpha v 

CD51

Binds fibronectin, vitronectin, fibrinogen, von Willebrand factor, thrombospondin and CD31 by dimerizing with a number of beta integrins

Integrin beta 3

CD61

Binds fibrinogen, fibronectin, thrombin and von Willebrand factor by dimerizing with CD41

Integrin alpha e

CD103

Binds E-Cadherin by dimerizing with integrin beta 7

Integrin beta 4

CD104

Binds laminin by dimerizing with CD49f

Integrin alpha 4 beta 7

LPAM-1

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.

Integrin

Human

Mouse

Rat

CD11a

MCA1848

MCA1368

 

CD11b

MCA551, VMA00481

MCA74, MCA711

MCA275, MCA618, MCA619

CD11c

AHP1226, MCA2087, MCA2786

MCA1369

MCA1441

CD18

MCA2086, MCA2510, MCA503

 

MCA775

CD29

MCA1189, MCA1949, MCA2028, VMA00063

MCA2298

MCA2298

CD41

MCA467

MCA2245

 

CD49a

MCA1133, VPA00569

 

 

CD49b

MCA2025, MCA2027, MCA743

MCA2125

 

CD49c

MCA1948, MCA5694

 

 

CD49d

AHP1225, MCA2503, MCA697, MCA923

MCA1230, MCA2082, MCA2294, MCA6063

MCA2872

CD49e

MCA1187

MCA2296

 

CD49f

MCA1457

MCA699

MCA2034

CD51

 

MCA2461

 

CD61

MCA2588, VPA00632

MCA2299

MCA2299, MCA1773

CD103

MCA1416, MCA708

MCA4705

 

CD104

MCA1456, VMA00285

 

 

Integrin alpha 7

MCA5238, VPA00525

 

 

Integrin alpha 9 beta 1

OBT1715, MCA1585

 

 

Integrin alpha v beta 5

5355-2657

 

 

LPAM-1

 

MCA6057

 

Featured Cell Adhesion Molecule Key Markers

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.

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).


Non-Integrin Cell Adhesion Molecules

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

CD Nomenclature

Ligand

PECAM-1

CD31

Homophilic interaction in endothelial junctions is disrupted by homophilic interaction with leukocyte CD31 during transmigration

CD34

 

Binds to L-Selectin on leukocytes

ICAM-1

CD54

Endothelial CD54 binds to LFA-1 or Mac-1 on leukocytes

E-Selectin

CD62E

Binds to the carbohydrate component of leukocyte glycoproteins such as ESL-1 and PSGL-1

L-Selectin

CD62L

Binds to GlyCAM-1, MadCAM-1 and CD34 on endothelium, facilitating leukocyte homing

P-Selectin

CD62P

Binds to PSGL-1 on lymphocytes

CD99

 

Homophilic interaction between CD99 expressed on leukocytes and endothelium plays a similar role in transmigration as CD31

ICAM-2

CD102

Plays a similar role to ICAM-1 in the binding of LFA-1 on leukocytes

VCAM

CD106

Binds to LPAM-1 on leukocytes

Basigin

CD147

Expressed on leukocytes and endothelium, interacts with several integrins

JAM-1

CD321

Usually exhibits homophilic binding on endothelial borders but can bind to LFA-1 on leukocytes during inflammation

JAM-2

CD322

An interaction with JAM-C, JAM-2  is able to bind VLA-4 on leukocytes

JAM-C

CD323

Usually exhibits homophilic binding on endothelial borders but can bind to Mac-1 on leukocytes during inflammation

MadCAM-1

 

Can bind to LPAM-1, VLA-4 and L-Selectin on leukocytes

LAMP-2 (MAC-3)

CD107b

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.

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

Human

Mouse

Rat

CD31

MCA1738, MCA1812, MCA4105, VMA00321

MCA1370, MCA2388

MCA1334

CD34

MCA1578, MCA547

MCA1825

 

CD54

AHP2183, MCA1615, MCA532, VPA00014

MCA1371

MCA773

CD62E

MCA1969, MCA5671

 

MCA6053

CD62L

MCA1076, VPA00599

MCA1259

 

CD62P

MCA2418, MCA2419, MCA2420, MCA796

MCA2419

MCA2419, MCA2420

CD99

MCA1850, MCA1919

 

 

CD102

MCA1140, MCA2290

MCA2295

 

CD106

VMA00461, MCA2237, MCA907

MCA2297

MCA4633

CD147

VMA00021, MCA1876, MCA2882

MCA2283

MCA729

CD321

MCA2269, MCA2270, MCA3827

MCA2346

 

CD322

AHP2452

 

 

JAM-C

MCA5934, MCA5935

MCA5934, MCA5935

 

MadCAM-1

MCA2096, MCA2320, MCA2321

 

 

Fig.3. Immunohistochemistry analysis of Human Cell Adhesion Marker CD31.

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.

Featured Cell Adhesion Molecule Key Marker 

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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