In contrast to ICAM-1 and ICAM-3, the functional role of ICAM-2 is not clear. Although it is constitut-ively expressed on most leukocytes and platelets, it is most strongly expressed on normal endothelial cells, and its expression is not modulated by inflammatory cytokines. ICAM-2 may thus serve a role in mediating the normal recirculation of LFA-1' lymphocytes in the absence of an inflammatory or immune response. Acting in concert with ICAM-1, ICAM-2 may also help to trigger further adhesion strengthening and transendothelial migration by-inducing an increase in the avidity of LFA-1 for all of the ICAMs. Combinations of anti-ICAM-2 and anti-ICAM-3 antibodies inhibit the mixed lymphocyte reaction (MLR), suggesting that ICAM-2, like ICAM-3, may help to initiate immune responses. Finally, ICAM-2 is the only known (3i-integrin ligand on platelets, which suggests that it might play a role in leukocyte-platelet interactions.

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