Leukocyte integrin ligands and the dynamics of rolling
THE CONTEXT
Leukocyte adhesion molecules bind specific endothelial ligands. Weak selectin interactions slow leukocytes so that they can recognize additional adhesion molecules.
Integrins and their endothelial ligands
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LFA-1, or lymphocyte function-associated antigen, is expressed on T lymphocytes and other leukocytes and binds ICAM-1 on activated endothelium. ICAM means intercellular adhesion molecule.
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MAC-1, or macrophage antigen 1, is expressed on monocytes and other leukocytes and also binds ICAM-1 on activated endothelium.
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VLA-4, a very late antigen, is expressed on T lymphocytes and other leukocytes and binds VCAM-1 on activated endothelium. VCAM means vascular cell adhesion molecule.
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The integrin designated a4b7 is expressed on lymphocytes and monocytes. Its ligand is MAdCAM-1 on endothelium in the gut and gut-associated lymphoid tissues. MAdCAM-1 means mucosal addressin cell adhesion molecule-1.
Cytokine induction and rolling
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Interleukin-1 and tumor necrosis factor induce endothelial E-selectin and the ligand for L-selectin. These cytokines are produced by tissue macrophages, dendritic cells, mast cells, and endothelial cells after encountering microbes or dead tissues.
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Selectin-mediated interactions have low affinity and a fast off-rate, so flowing blood readily disrupts them.
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Repeated binding and detachment produce rolling and slow leukocytes sufficiently for recognition of additional endothelial adhesion molecules.