ICAMs

ICAMs, or intercellular adhesion molecules, are members of the immunoglobulin superfamily of cell surface proteins that act as ligands for integrins and mediate leukocyte adhesion and transmigration. The best known members are ICAM-1 (CD54), ICAM-2 (CD102), and ICAM-3 (CD50). They are membrane glycoproteins with extracellular immunoglobulin-like domains.

Expression of ICAMs varies: ICAM-1 is inducible on endothelial and other cells by inflammatory cytokines such as TNF-α and IL-1; ICAM-2 is constitutively expressed on vascular endothelium; ICAM-3 is predominantly expressed on leukocytes.

Functionally, ICAMs primarily bind to integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) on leukocytes, mediating the capture, firm adhesion, and transmigration of leukocytes during immune responses. They also participate in immune cell interactions and synapse formation, particularly through ICAM-family interactions with antigen-presenting cells.

In addition to their role in normal immunity, ICAM-1 can serve as a receptor for certain pathogens, notably rhinoviruses that use it to enter cells. Soluble forms of ICAMs (such as sICAM-1) arise from proteolytic shedding and can be measured in plasma; elevated levels are observed in infections, inflammatory states, and some cancers, sometimes used as biomarkers.

Clinical and research relevance is centered on modulating leukocyte trafficking and inflammation. Anti-adhesion therapies targeting ICAM-1 have been explored but have faced limited success due to redundancy in adhesion pathways and compensatory mechanisms.