FIGURE 3.

Biological interactions mediated by integrins with ICAM-1 and TM. (A) During leukocyte homing to normal or inflamed tissues, integrin αLβ2 plays a key role by interacting with its cognate ligand ICAM-1 on EC, in mediating slow rolling, firm adhesion and trans-endothelial migration, or extravascular movement. (B) When T cells migrate to the extravascular space in tissue, they probe cognate antigen-presenting DCs and subsequently form stable and mature immunological synapses. In the immunological synapse, the interaction of αLβ2 with ICAM-1 builds up a distinct marginal region called the pSMAC; TCR and auxiliary molecules are enriched in cSMAC, which may empower T cells to become fully activated. (C) The β2 integrin on leukocytes (e.g., neutrophils) binds to the O-glycosylation-rich domain (D3) of TM on EC. This interaction may help counter-balancing inflammation by shifting adhesion from ICAM-1 to TM. EC, endothelial cell; DC, dendritic cell; TCR, T-cell receptor; pSMAC, peripheral supramolecular activation cluster; and cSMAC, central supramolecular activation cluster.