Table 2 Heterologous CAMs

Integrins

Integrin alpha (CD11a)

ITGAL (CD11A, p180)

Integrin alpha combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1). LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1–3 (intercellular adhesion molecules 1 through 3), as a rolling and signaling molecule[27], and also functions in lymphocyte costimulatory signaling.

ICAM1 (CD54)

ICAM1

A member of the immunoglobulin superfamily. A glycoprotein which is typically expressed on endothelial cells and cells of the immune system.

Integrin beta-2 (CD18)

ITGB2

ICAM-1 can be induced by (IL-1) and (TNFα) and is expressed by the vascular endothelium, macrophages, and lymphocytes. ICAM-1 is a ligand for LFA-1 (integrin), a receptor found on leukocytes.

Integrin alpha M (ITGAM)

ITGAM (CD11B, CR3A)

Integrin alpha M is one protein subunit that forms the heterodimeric integrin alpha-M beta-2 (α_Mβ₂) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3). α_Mβ₂ is expressed on the surface of many leukocytes involved in the innate immune system. It mediates leukocyte adhesion and migration.

Integrin alpha 4 (CD49d)

ITGA4

VLA4 (α₄β₁-integrin) is found on leukocytes and endothelial cells.

VCAM1[28]

VCAM1 (CD106)

VLA4-interections support lymphocyte rolling in venules of the central nervous system in conjunction with P-selectin or can directly mediate rapid adhesion independent of P-selectin engagement[27].

Integrin beta-1 (CD29)

ITGB1

Fibronectin

FN1

Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix[29]. Insoluble cellular fibronectin is a major component of the extracellular matrix. It is secreted by various cells. Fibronectin plays a major role in cell adhesion, growth, migration, and differentiation.

Altered fibronectin expression, degradation, and organization are associated with a number of pathologies, including cancer and fibrosis[30].

Integrin

α₄β₇-integrin

MADCAM-1

MADCAM1

MADCAM-1 is a cell adhesion leukocyte receptor expressed by mucosal venules. It helps to direct lymphocyte traffic into mucosal tissues. It can bind both integrin alpha-4/beta-7 and L-selectin regulating both the passage and retention of leukocytes. Isoform 2 lacking the mucin-like domain may be specialized in supporting integrin alpha-4/beta-7-dependent adhesion strengthening, independent of L-selectin binding.

Selectins

P-selectin

SELP

P-selectin is expressed on activated endothelial cells and platelets. Synthesis of P-selectin can be induced by thrombin, leukotriene B4, complement fragment C5a, histamine, TNFα or LPS.

PSGL-1 (P-selectin glycoprotein ligand-1)

SELPLG (CD16)

PSGL-1 is found on white blood cells and endothelial cells. PSGL-1 can bind to all three members of the selectin family however it binds to P-selectin with the highest affinity.

P-selectin plays an active role in the rolling of leukocytes[27].

see above and: PSGL-1 was shown contribute to E-selectin-mediated initial leukocyte capture and rolling in vivo[31].

E-selectin (CD62E, ELAM-1)

SELE (CD62E, ELAM-1)

E-selectin is expressed on activated endothelial cells. E-selectin is not stored within the cell and has to be

PSGL-1

SELPLG (CD16)

transported to the cell surface. Synthesis of E-selectin follows shortly after P-selectin synthesis, induced by cytokines such as IL-1, TNFα and lipopolysaccharide (LPS). Shear forces can also affect E-selectin expression. E-selectin may interact indiscriminately with many glycoproteins and glycolipids[31].

ESL-1 (golgi glycoprotein 1)

GLG1

ESL-1 is a glycoprotein and a variant of a receptor for fibroblast growth factor.

ESL-1 is a major E-selectin ligand on leukocytes[31].

CD44

CD44

CD44 is expressed in a large number of mammalian cell types. This protein participates in a variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis.

E-selectin was shown to play a pivotal role in mediating cell–cell interactions between breast cancer cells and endothelial monolayers during metastasis[32].

E-selectin plays an active role in the rolling of leukocytes[27].

The contribution of CD44 is significant only at the later stages of the leukocyte recruitment cascade[31].

GlyCAM-1

GLYCAM1

In breast cancer the splice variant 4 of CD44 was shown as a major E-selectin ligand in facilitating tumor cell migration across endothelial monolayers[32].

L-selectin (CD62L)

SELL (CD62L, LAM1)

L-selectin found on lymphocytes and preimplantation embryo. It plays important roles in lymphocyte-endothelial cell interactions.

GlyCAM-1 is a proteoglycan ligand expressed on cells of the high endothelial venules in lymph nodes.

CD34

CD34

A cell surface glycoprotein which functions as a cell-cell adhesion factor. It may also mediate the attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells.

Cells expressing CD34 are normally found in the umbilical cord and bone marrow as hematopoietic cells, a subset of mesenchymal stem cells, endothelial progenitor cells, endothelial cells of blood vessels but not lymphatics (except pleural lymphatics). CD34 is also an important adhesion molecule and is required for T cells to enter lymph nodes. It is expressed on lymph node endothelia whereas the L-selectin to which it binds is on the T cell.

MADCAM-1

MADCAM1

MADCAM-1 is a cell adhesion leukocyte receptor expressed by mucosal venules. It helps to direct lymphocyte traffic into mucosal tissues. It can bind both integrin alpha-4/beta-7 and L-selectin, regulating both the passage and retention of leukocytes.

PSGL-1

SELPLG (CD16)

See above