Intercellular adhesion molecule 4 (ICAM4)

Intercellular adhesion molecule 4 (ICAM4) is a 42 kDa glycoprotein exclusively expressed on erythroid cells and the red cell membrane. It is a member of the immunoglobulin superfamily, containing two extracellular immunoglobulin-like domains, and serves as the molecular basis for the Landsteiner-Wiener (LW) blood group system. ICAM4 mediates cell adhesion events critical for erythropoiesis, including the formation and maintenance of erythroblastic islands within the bone marrow by binding to multiple integrins, such as α4β1 (VLA-4) and αV-family integrins on macrophages and endothelial cells. Its interactions regulate processes like nucleus extrusion and apoptosis during red-cell maturation, and its elevated expression in sickle cell disease contributes to abnormal adhesion of sickled red blood cells, potentially exacerbating vascular obstruction and pain crises. While ICAM4 is not essential for red cell survival and its absence does not cause obvious pathology, it plays minor roles in blood compatibility and is occasionally implicated in autoimmune phenomena. No approved drugs currently target ICAM4 directly, though experimental peptides based on its integrin-binding domains have shown ability to modulate cell adhesion and erythrophagocytosis in vitro.

Other names

ICAM4LWCD242Landsteiner-Wiener blood group glycoproteinLW blood group proteinCD242 antigenLW antigen aLW blood group antigen aIntercellular adhesion molecule 4 (LW blood group)

For peptides/experimental antagonists: Blockade of ICAM4-integrin interactions (disrupts binding to integrins such as CD11c/CD18 or αV integrins to modulate adhesion and erythrophagocytosis)