L-Selectin

The smallest of the vascular selectins, a 74-100 kDa molecule, is constitutively expressed at the tips of microfolds on granulocytes, monocytes, and a vast array of circulating lymphocytes. L-selectin is also known as LECAM-1, LAM-1, Mel-14 antigen, gp90 ^mel, and Leu8/TQ-1 antigen. L-selectin is important for lymphocyte homing and adhesion to high endothelial cells of post capillary venules of peripheral lymph nodes. Moreover, this adhesion molecule contributes greatly to the capture of leukocytes during the early phases of the adhesion cascade. Following capture, L-selectin is shed from the leukocyte surface after chemoattractant stimulation. L-selectin interacts with three known counter receptors or ligands, MAdCAM-1, GlyCAM-1, and CD34. In conjunction with other molecules, L-selectin's function and influence in the adhesion cascade has been under scrutiny in many experiments using gene-targeted mice.

In L-selectin deficient mice, trauma-induced leukocyte rolling in mesentary or cremaster muscle veules is normal initially, but declines over time. Using an intravenous L-selectin antibody, this phenotype can be reproduced, thus blocking the function of L-selectin. This indicates that trauma-inducted rolling in these mice is P-selectin dependent with a velocity highly comparable to that observed in wild-type mice. L-selectin is critical in mediating rolling after surgical trauma and is necessary for neutrophil recruitment after inflammation. Nevertheless, basal neutrophil trafficking appears to remain unaffected by absence of L-selectin since peripheral leukocyte and neutrophil counts in these mice were normal.

In TNF-α, tumor necrosis factor-alpha, treated mice deficient in L-selectin, data suggests that leukocyte rolling is P-selectin dependent. The lack of L-selectin in these mice reduces the efficiency of E-selectin mediated rolling is shown by the sensitivity of rolling to P-selectin antibodies. These experiments consistently show that L- and P-selectin mediate leukocyte rolling, however, L-selectin alone cannot assume this task at normal velocities in vivo. L- and P- selectin cooperate in such a way that in the absence of P-selectin, L-selectin must initiate leukocyte interactions to allow slow rolling on E-selectin. In addition, L- or P-selectin must be present to mediate capture before the commencement of leukocyte rolling. Without the presence of either L- or P-selectin, rolling cannot occur.

Theoretical 3-D model of L-selectin (the C-type lectin domain, and residues 1-120). This 3-D structure is viewed using RasMol. Left-clicking on the molecule allows change in orientation, and right-clicking on the molecule gives options for different display modes.

To view the molecule using a different program, or to find out more information on the structure, choose P-selectin from the list of 3-D Structures of Selectins.

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